Rachel Wilson was a major character in the first season episode "The Party", then only appeared in some background shots in the second season. Eventually, she stopped appearing at all even in scenes that feature her other family members. Reportedly, several of the show's staff (including the show's creator) disliked her and her character design.
Molly Collins appeared in background scenes in the first season, before disappearing halfway through the second. Eventually, it was revealed that she had been taken to a nightmarish void in reality because the world itself deemed her boring and erased her from existence, only to be rescued by Gumball and Darwin. Afterwards, she made several more appearances, subverting the trope.
Likewise, Rob suddenly stopped appearing in the second season because of the same reasons as Molly. However, he wasn't rescued like her, and escaped by himself, horrifically disfiguring himself in the process. He then made several more appearances as a vengeful villain.
Debbie Hyman first appeared in Season 2 as the first girlfriend Steve actually managed to have for more than one episode, although their relationship came to an abrupt end at the end of her 2nd appearance a few episodes later. Aside from an indirect reference, she was completely absent for the following season. She later returned for "Escape from Pearl Bailey" and "Bar Mitzvah Hustle" where her and Steve made up and became a couple again only for them to once again break up but rekindle at the end of both episodes note Only happens in a deleted scene for the latter. To date, her only other appearances since "Bar Mitzvah Hustle" have both been in the milestone 100th & 200th episodes but only in brief non-speaking cameos presumably for both episodes to be filled with as many recognizable characters as possible.
Greg & Terry's daughter Libby was a pretty big part of the plot for her debut appearance in "Surro-Gate" and she would eventually go on to appear at least once in every season afterwards. Starting with the show's 11th season however, she's completely disappeared likely as a side-effect of her parents getting Demoted to Extra after Mike Barker (former showrunner and voice of Terry) left the series early into it's production due to creative differences which eventually resulted in Terry being Put on a Bus.
In American Dragon: Jake Long, Rose was separated at birth from both her parents and her twin sister to be raised by the Huntsclan. After the Huntsclan is erased from existence (long story) we catch up with Rose who in the revised timeline lives a normal life with her parents...and no twin sister. Apparently the sister's whereabouts would have been a plot point had the series been given another season.
Several characters in The Animals of Farthing Wood who weren't killed off, but simply disappeared in Season 3. this includes Fox and Vixen's son Friendly, Kestrel, and the surviving blue foxes aside from Ranger. Friendly made a brief appearance in the second episode of Season 3, then was absent for the rest of the series without explanation. Word has it that the show's producers didn't like him and requested that he be dropped from the show. Kestrel's disappearance is actually consistent with the original novels, in which the character simply stops appearing around the fifth book in the series, with no specific departure arc.
Lampshaded in an episode, where Rita and Runt are advertised as "Missing" on a milk carton (the "Rita and Runt" segments having been dropped in the latter half of the series' run, after which the characters themselves put in the occasional cameo appearance, but gradually disappeared - though they continued to feature in the opening credits, and were eventually restored for the direct-to-video movie "Wakko's Wish").
Minerva Mink's disappearance was more justified. Her cartoons were too risque, even by Animaniacs standards — of the two that actually aired, one had a nerdy werewolf who turned into a hunk under the full moon; the other had Minerva using her sex appeal to dispatch a dachshund named Newt — and the executives were afraid she'd be used in a lot of sexually unsavory fan art and fanfiction online. This ended up being a fool's errand, as this became Minerva Mink's fate anyway, thanks to those two episodes. It would have been easier to not have made Minerva a character in the first place.
In a couple of episodes George has a sister who is around his age; she last appeared in the Christmas special and so far has not appeared again.
There's D.W.'s pet toad "Toady" from season 1. When she reappeared in season 7, it is implied that she has simply been living in the yard. She's gone again until 7 seasons later, but this time her disappearance is justified in-universe because she is now married to another toad.
Mrs. Fink and Miss Sweetwater (the other 3rd grade teachers) and their respective students, were occasionally featured in the early seasons, mostly to act as a foil to Mr. Ratburn and his students. They have consistently shown up as background characters, though.
While not trulyChuck Cunningham Syndrome, Jenna the cat was much more of a major character in the earlier seasons (even receiving her own episode at one point), only to fade away as the series went on; she almost never even appears as a background character now.
In the TV series for Barnyard, titled Back at the Barnyard, Otis' wife, Daisy, and their son Ben Jr. are completely absent from the show, Daisy's been replaced by a new female cow named Abby, who is more of a rough-and-tumble tomboy who readily stands up to a threat and is treated equally amongst the guys; the strange part is Daisy's best friend Bessie continues to appear on the show. There was also a the donkey from the movie that disappeared.
In Walter Lantz's The Beary Family, the family originally consisted of Charlie (father), Bessie (mother), Junior (son), Suzy (daughter), and their pet goose, Goose. Early into the series, Goose disappeared, then eventually Suzy was dropped without explanation.
Bimbo the Dog from the Betty Boop cartoons. In the early shorts he was meant to be Betty's boyfriend, but come 1934, and the Hays Office objected to an interspecies relationship, forcing Fleischer Studios to abruptly drop Bimbo. He would never be seen again in the series.
In the 2006 revival of Biker Mice from Mars, pretty much all major characters from the original 1993 cartoon are accounted for. Lawrence Limburger, Dr. Karbunkle, and Greasepit even appear a couple of times in spite of the Catatonians and Ronaldo Rump replacing them as the main villains. The one character who doesn't return, however, is Karbunkle's deformed and masochistic assistant Fred the Mutant, though he does have a brief cameo in the three-part episode "Once Upon a Time on Earth".
In Blazing Dragons, Sir Galahot and Sir Hotbreath, two of the Knights of the Square Table, never appeared in Season 2, in which the main focus was on Flicker, Loungelot, Blaze, and Burnevere, but Allfire, Griddle, Flame, and Count Geoffrey and his minions all had some appearances.
In The Blue Racer, the main character chased after a racially insensitive Japanese Beetle (yes, a racist Japanese caricature depicted as a beetle). The Beetle character was dropped halfway through the series. Gee, I wonder why...
Officers Julia and Cliffany from Bob's Burgers suddenly disappeared after Season 1, but they did make a few non-speaking background appearances in some episodes.
In Chip 'n Dale Rescue Rangers there was one episode where Dale falls in love with a bat named Foxglove, who loves him back. Chip is also happy because he gets Gadget all to himself. Foxglove was never seen again, though she seems to appear in more Fan Fiction than not.
Disney Afternoon shows regularly only had a small number of recurring characters while most other characters, even main characters are limited to one episode. These one-shot characters, however, sometimes gained a lot of popularity and fans of their own, sometimes more than some main characters. Chip 'n Dale Rescue Rangers had some more popular one-shots including the squirrel Tammy, the lab rat Sparky, Gadget's Evil Doppelganger Lahwhinie and Gadget's father Geegaw who is only ever seen in a picture. This popularity mostly rose long after the show was produced in a time when there was neither a vocal fandom nor an appropriate means of communicating the popularity of a character to the makers, so none of them ever returned. Both Foxglove and Geegaw eventually returned in the Boom! comics.
Semi-justified because her actress, Billie Lou Watt, died around that time.
In The Critic webisodes, ALL the characters from the TV series have disappeared (save Jay Sherman and a brief appearance by Vlada). The worst of all this is that Jay's girlfriend Alice Tompkins is replaced with a Replacement Scrappy named Jennifer.
Several characters from the Curious George movie who played fairly big parts like Maggie, Mr. Blooms berry, and Junior are nowhere to be seen in the TV series.
After the episode "Trick or Treehouse", Mee Mee and Lee Lee were no longer seen or mentioned (although they were generally carbon ethnic copies of Dee Dee anyway).
Mandark's sister Lalavava, was never seen or mentioned after her appearance and the later seasons seem to depict Mandark as an only child.
Action Hank and The Pony Puffs (Dexter and Dee Dee's heroes, respectivly) also seemed to have taken their leave after Season 2.
Then there's Douglas P. Mordechai III, Dexter's friend from the schoolbus. He only appeared in three episodes. Justified in that few episodes from Dexter's Lab took place at school.
Dora the Explorer showed that Diego had an older sister named Daisy. She was replaced with Alicia once he got his show, even though the episode she was in revolved around her birthday. In Go, Diego, Go!, she's said to be in college and she was mysteriously aged up.
The second episode of Nickelodeon's Doug, "Doug Can't Dance", had Roger leading a different group of thugs than usual. These thugs appeared only in that episode. Justified in that "Doug Can't Dance" was the series pilot.
DuckTales notably had quite a few recurring characters disappear without any explanation during its second season, including Doofus, three of the Beagle Boys (Bankjob, Babyface, and Bugle), and Donald Duck and Admiral Grimmitz.
Ewoks There's Paploo, a prominent character in the first season. In the second season, he was reduced to a non-speaking cameo and the leading four do not even seem to notice his absence from their adventures.
Remy Buxaplenty, rich bastard and Juandissimo's godchild is an odd example of this in that he is written out of the show at the end of his first appearance. Three seasons later, apparently due to viewer demand (and because he was one of the creator's personal favorite characters), he returns as a recurring antagonist to Timmy for three more episodes. After the third one, though, he's not mentioned again, not even in Juandissimo's subsequent appearances. He actually appeared in a much later episode called "Country Clubbed", except with a redesign and a minimal role.
Back when Mark Chang was Timmy's enemy he had two friends on Yugopotamia named Jeff and Eric. They haven't appeared recently, not even in an episode that had Mark going back to his planet temporarily.
This might be the fate of Trixie Tang & her "friend" Veronica as of season 9. Trixie has occasionally appeared in the background but she doesn't speak as her voice actress left and she hasn't been replaced.
Although not a straight-up example, after the first live-action movie, Tootie stopped appearing in the series proper and became relegated to the live-action movies only, which are still ambiguously canon.
The Team Pet Sparky was introduced in season 9 but doesn't appear in season 10, even in a non-speaking cameo. There's no in-series reason for his exclusion. He was removed due to poor reception and likely won't return in future seasons.
Even outside of the many incidental cutaway characters, Family Guy has a few.
The trope is directly lampshaded in the episode "The Father, the Son and the Holy Fonz", in which Peter starts a religion based on Happy Days.
Peter (preaching): Let us contemplate the mystery of Richie’s older brother Chuck, who ascended the stairs with his basketball in season one, and never came down again.
Brian's gay cousin Jasper, who used to appear a couple of times per season, disappeared after the gay marriage episode.
Jasper appeared in the episode "Brian's Play" talking with Brian on Skype and the episode "Life of Brian" at Brian's funeral.
Joe Swanson's own children seem to disappear without a trace. Kevin Swanson appeared in the first 3 seasons, then just disappeared for years, though he had a few non speaking cameos. Years later after his last speaking role Peter questioned about his disappearance out of curiosity. Joe explained Kevin died as a soldier in Iraq with hardly any emotion. Seth MacFarlane felt Kevin was not a very interesting character to write for. Kevin is brought back in "Thanksgiving", where it's revealed he faked his own death and deserted after witnessing the horrors of war in Iraq.
Parodied in "Spies Reminiscent of Us" when Chris enters in an exchange program to be replaced for an Elephant (don't ask). at the end of the episode Brian stated that it was a joke for the episode.
In Carol Pewetershmidt's first appearance she had just given birth to a baby boy, in her recent appearance he is nowhere to be seen.
Chris was set up to be with a girl named Anna in "Long John Peter" but, after that episode, she's never mentioned again and Chris is seen trying to get with other girls after that. That also happened with Herbert's niece in the Valentine's Day episode.
Knowing who voiced Anna (Amanda Bynes) there is no way she will return to the series!
Due to the changing nature of the franchise The Flintstones offers some changes:
Upon the aging up for The Pebbles and Bamm-Bamm show, Dino, Hoppy and the Great Gazoo were gone, new pets in their place.
During that shows new episodes the new pets are gone but Dino is back
In The New Fred and Barney Show, all the pets are back. Gazoo was still gone.
Franklin is rather bad for this, but perhaps the worst example is the character of Moose. An entire story in the first season of the program, based on of the books, was dedicated to introducing this character and his acceptance within the close-knit community. In the episode, he finally joined Franklin's class and became his good buddy, but he was never again seen on the series and no explanation whatsoever was provided for his absence.
Lampshaded in the second season of Freakazoid!. Lord Bravery, Fanboy, and the Huntsman are upset about their sequences being trimmed down to nothing in the second season and want something to do. Freakazoid makes them wash his car and that's the last we ever see of them.
Ironically, Freakazoid's alter ego, Dexter Douglas is only seen twice in the second season and never shows up again.
The DiC seasons of G.I. Joe quietly wrote out the Crimson Twins (Tomax and Xamot), with no word what happened to them after the movie, other than that their business was shut down.
Hey Arnold! had a few. Anybody remember Ruth P. McDougal (the sixth-grade girl Arnold had a crush on, though she could have graduated. She wasn't seen much after the Valentine's Day episode where Arnold tries to go on two dates at once and finds that Ruth isn't the dream girl he thought she was, as she was very boring, very shallow, and not very bright) or Mr. Smith?
The first episode with Coach Wittenberg mostly revolved around his son, Tucker, and Arnold helping him get his father's approval. Tucker vanished after that, even though Coach Wittenberg continued to appear, along with the introduction of his (ex-)wife Trish (presumably Tucker's mother?) Tucker didn't even show up when the two remarried.
Harvey the mailman is pretty much one. He appeared regularly from 1996 to 1999, but by the Turn of the Millennium, he hardly ever appeared on the show, making only background appearances here and there. For unknown reasons, Harvey's voice actor Lou Rawls stopped doing voice work for the show after the Season 4 episode "Chocolate Turtles."
Ludwig, a bully who competed with Wolfgang in his single episode never appeared again, despite him becoming friends with Wolfgang at the end of the episode.
Torvald disappears after only three episodes (the last of which is only a brief silent cameo).
I Am Weasel's sexy nurse, Loulabelle, made her debut in the season 2 premiere, but was not seen or mentioned since the season 3 premiere. It was already implied in one episode that she didn't like Weasel, so that's one reason. The more likely reason was Cartoon Network didn't approve of the dumb blonde stereotype she perpetuated, or because she was too similar to Hello Nurse.
Odd since one of the main characters in Ed, Edd 'n' Eddy was one (Nazz), though she doesn't show up as frequently as the other characters.
In the 1980's The Jetsons revival, shortly into the run Elroy got a pet alien named Orbity who he hatched from an egg and was the last of his species. He made regular appearances throughout the series until the season 2 finale "A Jetsons Christmas Carol", after that he was dropped from the series and was never seen again, not even in the movie.
Johnny Bravo had Jungle Boy, a character who appeared in several episodes of the first season (and may have been intended to star in a backup feature like The Justice Friends or I Am Weasel), but who vanished come the second season and the retool the show underwent. Not even the fourth season, which brought Van Partible back, had him featured at all.
Similarly, Pops disappeared when Van Partible returned. Carl met a luckier fate, demoted to occasional cameos.
In the Jumanji cartoon, the villainous "Stalker" character was introduced in the sixth episode, who looked somewhat like the Grim Reaper. The other villains feared and worked for him, which seemed to be setting him up as the main villain of the series. Unfortunately, he only appeared in two episodes and never reappeared, despite the ending of both episodes hinting at a reappearance.
In the second season of Jungle Junction, Carla the koala vanished completely.
KaBlam! had a number of these. Sniz and Fondue's room mates, Bill the Lab Guy's daughter Quirky from Action League and Grubby Groo from The Off-Beats (The only adult in that entire short!).
Eventually mid-season 3, Sniz and Fondue themselves were Chucked- the creator of the shorts left Nickelodeon due to studio politics. The Off-Beats themselves also got the treatment after the second season.
Life With Loopy had Stacey, who had first appeared in "Larry's Girl" at the end of the third season as Larry's girlfriend, setting her up for more appearances. By the time season four came around, she was nowhere to be seen and was never mentioned once (though Larry going Out of Focus that season might have had something to do with it). Larry's favorite TV stars, Charlie Chicken and Turkey Thompson, also disappear in the fourth season after being semi-regulars in the first three seasons.
Star quarterback Brick Flagg from Kim Possible showed up here and there, but he sort of vanished after a while. Although his no longer appearing was eventually justified at least for the last season, he graduated by then. He wasn't exactly the brightest bulb when off the football field, and it was mentioned that he'd finally graduated after being held back a few years. (He even votes for one of his opponents during the school election. Not that it mattered much.)
Zita, a Ron's love interest, disappear after her second appaerence without no mention of her by the main characters. She return in the Grand Finale as Felix's girlfriend.
Several recurring characters in King of the Hill just disappeared over time like Eustace and his geeky son Randy, who were rivals to Hank, Bobby and their friends in the earlier episodes but they vanished over time too. Bill's iguana Lenore only makes a one-episode appearance, and his girlfriend Laoma, who was Kahn's mother. A season finale episode ends with her living with Kahn and her and Bill in a relationship, but come the new season she's inexplicably gone. The writers apparently wanted to keep Bill alone and miserable.
In the episode in which Bobby breaks up with Connie, he meets a new girl named Debbie at the mall. They get along fine and are set up to be a couple; come next season she is never seen nor mentioned again and Bobby is back to being single. This happened quite a few times, actually: Bobby would meet a new girl who clearly liked him and they are seen together at the end of an episode. Invariably the girl is never seen or mentioned again because Bobby must always lose when it comes to romance.
Theres also the blonde kid Garth, who appears in the Straight Arrow episode and is implied to be Boomhauer's illegitimate son.
In the second episode, "Square Peg", Peggy is seen talking to several other women on a bench at a Little League game. Come the next episode, they have vanished and Peggy's only friend is Nancy. This may have been a retcon for later episodes that had Peggy worried that she didn't have enough female friends.
Those women do appear in the episode in which Khan and his family move in three episodes later but as mentioned previously they don't appear again after that.
Those women appear again rather infrequently and at times not all together, one episode in season 2, Peggy's Turtle Song features them delivering a very bizarre Laughing Mad moment.
The cartoon was based chiefly on the original game in the series, with bits of Zelda II: The Adventure of Link. Despite being a prominent part of the backstory for both games (indeed, she was the reason Link took up his famous quest in the first place), Zelda's nursemaid Impa is not included in the cast. She did, however, feature prominently in the comic book series which launched at approximately the same time.
Also, the Triforce of Courage is never mentioned in the animated series either (the Triforces of Power and Wisdom can count as characters; they even have voices!). As with Impa, Courage is mentioned in the comics and other books (though never seen; it is said to be "in Link's heart") that were otherwise similar to the cartoon.
Almost all of the original Pre-Daffy DuckLooney Tunes stars (i.e. Bosko, Buddy, Porky Pig's friends) have been missing from the series for decades. This is probably understandable, as Bosko does look like a racist caricature of an African American, as was prevalent in the pre-civil rights era, and other characters from the era (especially those preceeding the Hayes Code) would be considered too risque or violent for today's audiences.
Tiny Toon Adventures brought Bosko, Honey, Foxy, Foxy's girlfriend and Goopy Geer back for cameos, in which they were hailed as talented veteran cartoon stars. Later, an episode of Animaniacs had Buddy make an appearance, but it was a lot less complimentary toward the character in question (turns out Yakko, Wakko and Dot were created just to spice up his notoriously boring cartoons, but they were ''too'' looney).
Bosko, the original Looney Tunes star, very rarely makes appearances in modern Looney Tunes artwork, and hasn't appeared in any cartoons since his redesigned cameo in Tiny Toons. Understandably, this is due to his roots as a blackface character making him an unacceptable character to put into the mainstream today. It dosen't help that his esoteric nature compared to the mainstream Looney Tunes (due to his cartoons being off the air since the 1980s), not to mention his vague personality, do not make him a popular character among fans.
In the Seven Arts-era during the late '60's, some new characters were introduced, such as Cool Cat, Merlin the Magic Mouse and Bunny & Claude. While Cool Cat and his rival Colonel Rimfire often appear in modern Looney Tunes works, Merlin (and his partner Second Banana) and Bunny & Claude haven't really been seen since the Seven Arts-era.
Twist is shown as Apple Bloom's best friend in "Call of the Cutie". They have a bit of fallout when Twist gains her cutie mark while Apple Bloom doesn't (Twist even says "We can still be friends, right?"), and for the rest of the show Apple Bloom is spending all her time with her new friends, Sweetie Belle and Scootaloo, and forming the Cutie Mark Crusaders with them. She does appear in the background, but has not had a speaking role since. And since her voice actress moved sometime after the episode, this is not likely to change.
Averted with Princess Luna. After her release from her Super-Powered Evil Side (hinted at Demonic Possession) Nightmare Moon, in the second episode, Celestia says they will rule Equestria together. However, Luna does not appear or is even referenced in any later episodes of season 1. In season 2, however, she is mentioned in the two-part premier, and only two episodes later returns in an episode that revolves around her, and has appearances in the finale, and even more appearances in seasons 3, 4, 5 and 6, so for season 1 we can say she was Put on a Bus instead.
Slightly averted with Queen Chrysalis. She has not returned since falling over the edge of Canterlot in the season 2 finale, except in the comics. While the reason for her absence can easily be guessed by those willing to accept it, she is not referenced again in the show, unlike the other villains (many references to Nightmare Moon are made, Discord returns and does a Heel–Face Turn, Rainbow Dash makes reference to King Sombra while Twilight uses his dark magic, the season 5 premiere has Rainbow Dash mention Tirek, and Starlight Glimmer also undergoes a Heel–Face Turn). However, the Journal of the Two Sisters shows that Twilight's full friendship report for "Three's A Crowd" mentions Chrysalis during the part about the fate of Equestria hanging in the balance the last few times Twilight saw Princess Cadance. She reappears in The Cutie Re-Mark, Part 2 in an alternate timeline and reappears again as a Big Bad in the season 6 finale To Where And Back Again.
Likewise Babs Seed who showed up in Season 3 for two episodes with the implication that she was going to be a Sixth Ranger to the Cutie Mark Crusaders. However after her second appearance, she never shows up again and most mention of her was in season 5 where we learn she got her cutie mark off screen. Apparently her voice actress had left the show and they didn't want to replace her our of respect, so instead just didn't have her reappear. The comics do utilize her a bit more though.
My Little Pony 'n Friends had an ever-changing cast, as they tried to market as many ponies as possible. There were some characters that never faded like Wind Whistler or Fizzy but others disappeared without a trace:
Notoriously none of the ponies from the first special ever pop up again. You'd think they'd have a close bond to Megan or would at least pop up more, considering they saved the entire kingdom. Whenever the ponies go snatch Megan, she never says "Where's Firefly? Or anybody who was here last time?" It's especially unusual for Firefly to never appear as she was more-or-less G1's mascot.
It's most notable with the "baby" versions of several ponies. It's not 'til the TV series gets underway that they're treated like the toyline treats them (as daughters of the adult ponies they're named and designed for, existing alongside them.) This introduces a serious hole to the second special: it has has baby versions of two characters from the first special and two who will appear in future installments. If those are their daughters, then how come they're never, ever seen alongside their mothers? (Of course, maybe the ones whose adult versions were yet to appear are the same characters grown up; at least, that's how the fandom treats it.)
Popeye had four nephews introduced around 1940 - as the series went on it was knocked down to three, then two. This was probably due to animation cost restraints, but it comes off as pretty creepy.
Hanna-Barbera's take on Popeye in 1978 brings back three of the nephews. But in 1987's ''Popeye & Son," the nephews and even Swee' Pea are egregiously left out in favor of Popeye and Olive having a son.
On the British animated sketch show Planet Sketch there was a character named June Spume whose gimmick was that she could transform her body parts into musical instruments and play them. She didn't return for the second season, possibly because the writers ran out of ideas for her.
The 2016 revival of The Powerpuff Girls explicitly does this to Ms. Sara Bellum, the Sexy Secretary and brains behind the Mayor of Townsville, which otherwise having almost all of the original series' characters return in the revival. The in-universe reason is that Bellum's worked diligently enough without taking any time off that she earned a ridiculously large amount of vacation time (as in years worth). However, the actual reason was that "she wasn't quite indicative of sending the kind of messaging we wanted".note Which is considered by fans as a strange decision since A) the revival is more "Girl Power" focused, and, since Bellum was always an intelligent and capable woman, she'd actually assist in the revival's overall focus by showing that she was more than just a pretty... er, face, and B) removing her suggests that the showrunners ultimately didn't see beyond her attractive design (despite acknowledging her good traits), which sends the message that her appearance would undermine any and all of her positives.
In Rocket Power, the Rocket's neighbors, the Stimpletons, appear a lot less in Season 3, almost to the point of cameos, actually. Also, how often do you see Mackenzie during that season, either?
In the original run (1991-94) of Rugrats, two slacker teenagers named Larry and Steve were seen from time to time with a different job in every appearance. After the show's hiatus, they disappeared; in a later episode, Larry appeared as a donut salesman - after that, he was never seen again.
Scooby Dumb appeared in four Scooby Doo show episodes and as a regular in the Laff-A-Lympics and that was it
Fred, Daphne and Velma disappeared in the 80s without explanation, but for those that did keep watching all three were told of where they went. They did finally make an appearance in a Christmas special.
After The Movie and a brief appearance in the opening of the 19th season premiere, Colin was never seen again and Lisa is back to being single. Yeardley Smith actually voiced her annoyance at this, arguing that Lisa deserves "to keep this one."
Lionel Hutz and Troy McClure were both retired after their voice actor Phil Hartman's untimely death. Since 1998, they've disappeared from Simpsons canon (with the very occasional exception of a crowd scene). Hutz's role as the Simpsons' incompetent family lawyer was taken by 'Old' Gil Gunderson.
Dr. Marvin Monroe, who appeared as a recurring character in the first six seasons of the show. In reality, his character was officially retired by the seventh season due to his voice being murder on Harry Schearer's throat. The in-universe explanation given was that Monroe had died. He returns in the episode "Diatribe of a Mad Housewife" at Marge's book signing, where Marge is shocked to see he's alive. This trope is lampshaded, with Dr. Monroe giving the explanation "Oh, I've been very sick".
Early episodes had two - almost identical - characters called the Weasels do Nelson Muntz's bidding. Sometime around the third season, they disappeared and Nelson became friends with the Jimbo, Dolph and Kearney trio. The producers explained on the DVDs that six bullies felt like too many. They made their first appearance in years in "The Winter of His Content", where it's revealed they moved to Shelbyville.
Homer's half-brother Herb seems to be this as well. He made appearances in two early episodes, then never appeared again. The series occasionally will quip about this, such as once when Homer makes a passing reference to "my seldom-seen half brother Herb." Herb makes a speaking cameo on Homer's answering machine in Season 24's "Changing of the Guardian" in which he reveals that he is poor again.
The secondary Channel 6 newscaster Scott Christian was quietly phased out after Kent Brockman became recognised as the much funnier character. Ironically, a running gag was suggested that Christian would always be covering for a perpetually absent Brockman, despite the Action News show being named after the latter. One instance of this was trialled in season 1's "Krusty Gets Busted", but was soon rejected, and Brockman does actually appear later in the same episode.
Serak was in the first Treehouse Of Horror along with Kang and Kodos, who appeared in all subsequent Treehouse Of Horror episodes, but Serak didn't. This is because "he costs money," being voiced by James Earl Jones.
Herman, first seen in Bart The General, was supposed to be a recurring character, his gimmick being that each time he showed up he'd give a different story of how he lost his arm. Aside from a few cameos, he's never been seen again, and how he lost his arm was resolved in a flashback episode.
Sideshow Bob's Italian wife and son disappeared after their second appearance in "Funeral for a Fiend" with no mention of where they went (for the record, Bob has appeared several times since).
Tweek was removed from the classroom scenes in season 15. Pip had preceded him in nearly being completely written out, although he was brought out for one last brief cameo in "201". He was brought back as a focus character for "Tweekx Craig" in Season 19, and he was the focus of a sidequest in The Stick of Truth, so it looks like the writer's haven't forgotten about him outright.
Nurse Gollum from season 2 (other than a voiceless cameo in "Freak Strike"). However, there's a good explanation for why she was removed from the show.
Dr. Mephesto and Kevin. They were main characters in the first 3 seasons, but disappeared early on in the fourth. One of them DID, in fact make, a one-off apperance in 201 but has not been seen since. Parker and Stone have stated, however, that they grew tired of Mephesto and had wished they'd written him off completely in season 4.
Some of the children's parents that aren't Stan, Kyle, Kenny, Cartman, Butters, Token, Wendy, etc, have been replaced with different people.
Midget Wearing Bikini and other joke news reporters seen in the earlier seasons were phased out in favor of just using "Tom" or parodies of actual reporters.
Mephesto's son Terrance was introduced as The Rival to the four boys, along with his sidekicks Bill and Fosse. Terrance quickly faded into the background, as did the other two (barring a cameo in the Season Seven episode "Li'l Crime Stoppers"). The three are still occasionally seen as background characters, but lack their signature thick eyebrows. Craig, Clyde, and assorted other boys now play the part of the rivals to the main four.
Mr. Wyland, the substitute teacher.
Officer Barbrady: Effectively replaced by a full police force around season 7, though he is still brought back for small appearances every now and again.
Lampshade Hanging in "Cartman's Incredible Gift" when Ms. Crabtree is murdered by a serial killer.
Lou: "I owe it to that victim over there! I know she hadn't been in any recent episodes, but DAMMIT, she deserved better than this!"
Damien hasn't reappeared in years (aside from background cameos in the gymnasium at times, or being seen on a TV in "Tsst!") despite his father making numerous reappearances.
Nurse Goodly (the nurse with no arms from "Cartman's Mom Is Still a Dirty Slut") hasn't made a reappearance in scenes taking place in Hell's Pass Hospital.
Fluffy, Cartman's pet pig, hasn't been seen since the episode "Cherokee Hair Tampons" all the way back in season 4.
On Space Ghost Coast to Coast, much of the Council of Doom disappeared without a trace. The most obvious examples are Metallus and Black Widow. Lokar disappeared after "Waiting for Edward", and after "King Dead", Tansut was never seen again.
The Creature King suffered this the worst. He was closest thing the sixties series had to a Big Bad. He was the main head of the Council of Doom and fought Space Ghost more times than any other villain. Yet he never appears in Coast to Coast, unless you count stock footage from "Jacksonville".
Stereo was written out of the second season of Space Goofs. Only to reappear in two episodes.
In some of the earlier episodes of SpongeBob SquarePants, SpongeBob had a pet scallop in a bird cage above his bed. He was never seen interacting with it, though, and during the middle of the second season it vanished. This was referred to in one of the video games when in SpongeBob's room when you click on the cage, he says something along the lines of "That's where I kept my pet scallop, I think he ran away". Which is weird, in that it has been seen in later seasons, too. Apparently his runaway scallop got homesick and decided to come back.
Bubble Bass appeared to have suffered this fate, being in a couple episodes back in season 1 and then disappearing. Apparently he was simply placed on a very long bus ride, because he had an appearance in the Season 8 episode "Plankton's Good Eye", and then made a cameo in the second movie.
Flatts the Flounder, who was the bully at Mrs. Puff's Boating School. He only appeared in three episodes - one of them where he made a major role - and never appeared after that.
Squilliam Fancyson hasn't made a single appearance since Season 7.
In SWAT Kats, we have a couple of examples. In all cases, the characters are likely still there, somewhere in Megakat City, but just never focused on.
Feral's second-in-command Steel. He is last seen being chewed by Feral in "Enter the Madkat", and never reappears in the second season. It's been argued that Feral's niece, Felina, replaced Steel as her uncle's second in command, however they have different ranks and uniforms - Felina is only a lieutenant and Steel was a lieutenant commander.
Burke and Murray. Last seen briefly in "Metal Urgency", they are never seen or mentioned again. The main reason for this seems to be the lack of any scenes focusing on Chance and Jake's civilian lives in the second season, and since Burke and Murray were created to antagonize the two in those scenes, when they went, so did Burke and Murray. The two were slated to appear in an episode that never got made, though.
Al the Kat's Eye News helicopter pilot. He's last glimpsed in a non-speaking role flying the copter in season one's Chaos in Crystal, and although the helicopter itself appears multiple times in many other episodes, Al himself is never seen again. However, considering someone has to be flying the aircraft, he is probably still there.
Dr. Street is last seen getting knocked out of a window in The Ci-Kat-A. He presumably could've saved himself by using his wings to fly to safety, and, indeed, this was what the writers had in mind, as they wanted him to return in another episode and team up with Dr. Viper, but the series was cancelled before the episode was finished.
Dr. Viper himself. After turning himself into a giant monster in Mutation City, he gets doused with anti-mutagens and disappears from both the episode and the series. His final appearance is in The Origin of Dr. Viper, but that's told entirely in flashback. As mentioned above, though, he was scheduled to reappear in an episode alongside Dr. Street, but then the show was cancelled.
Bizarrely, the SWAT Kats' own arch-enemy Dark Kat. He gets away at the end of Razor's Edge in season two, vowing to return, but apart from an alternate universe version of him in The Dark Side of the SWAT Kats and a cameo as a cardboard cutout in The Origin of Dr. Viper, he never reappears, nor do any of the known unfinished episodes involve him.
In an example of Early Installment Weirdness, there are a lot of reporters besides Ann Gora seen in The Giant Bacteria, including two male reporters from Kat's Eye News and two from a different news channel called Inside Megakat City. Both male Kat's Eye News reporters get to interview Feral in two different scenes, but after this episode, neither they nor the other reporters appear again. Inside Megakat City vanishes and Kat's Eye News is apparently the only news channel of any importance in town, and, aside from one brief appearance by Tab Mouser (who vaguely resembles one of the reporters from The Giant Bacteria) in Unlikely Alloys, Ann Gora appears to be its only reporter!
In the second episode of volume one of RWBY, Yang abruptly leaves Ruby shortly after arriving at Beacon to "go catch up" with her other friends, who are seen briefly as four black silhouettes. Despite Yang getting plenty of screen time as a main character and making many other friends throughout the show, these particular friends are never seen or mentioned again.
In the final season of Teen Titans the Brotherhood of Evil recruits nearly every villain that ever appeared in the series. While the appearance of some in the initial lineup is a Snapback from the last time they fought the Titans, some such as the Nufu Source didn't appear in the final battle while Kitten wasn't seen after her encounter with Starfire.
Both of which can be easily explained - Kitten was just a spoiled brat, and Cyborg ATE the Nufu Source. However, some of the villains that the Brain called were actually killed somehow.
Speaking of the Brotherhood of Evil; the Doom Patrol, who were the Brotherhood of Evil's original enemies in the first place, are basically written out after "Homecoming Part 2". What happened after the Titans intervened? The Brotherhood of Evil basically focused on getting rid of the Titans. The Doom Patrol weren't even there to help, nor they were mentioned.
In the first episode, arch-villain Slade is always seen with a silent butler standing at attendance - possibly Wintergreen, Slade's butler in the original Teen Titans comics. He is never seen with Slade after this episode, but if you look quickly, he is seen with the Brain's group of villains. (Word of God says that Slade was uninterested in joining but sent Wintergreen as his representative.)
The H.I.V.E. Academy Headmistress was a bizarre example, as her first (and until the series finale, ONLY) appearance, she seemed to be set up as a Big Bad in charge of training teen supervillains. When the H.I.V.E. organization resurfaced in later seasons, she had been usurped by Brother Blood with no real mention of what happened to her. She returned in the series finale as part of the big final showdown but was quickly dispatched. She later appeared in the comic alongside a new trio of teen villains, but was quickly Bound and Gagged by Robin and presumably arrested. In all of this, it was never explained exactly what had happened that lead to her being booted from her position at the academy.
In the original Teenage Mutant Ninja Turtles cartoon there was an episode involving a female lizard mutant named Mona Lisa. She serves as a potential girlfriend for Raphael and helps him fight off hijackers who were responsible for her mutation (she was originally a human); at the end they say their goodbyes and she secretly follows Raphael and April to the turtle's lair and introduces herself to the rest of them. Despite this being a setup for her being a recurring character and being a fan favorite she is never seen or mentioned again.
That cartoon used to pull the same schtick all the time. They'd have an episode that seemed to set up a new cool character, then they'd usually disappear forever. Remember Metalhead? And Muckman and Joe Eyeball?
Several notable recurring characters, some of which had been on the show from the beginning, just disappeared during the show's 7th and 8th seasons. Season 7 saw the final appearances of the friendly teenage aliens the Neutrinos and the Turtles' young friend Zach. In season 8, Irma, Vernon, Mr. Thompson, and Casey Jones made their last appearances and then vanished without explanation. Bebop and Rocksteady disappeared after season 8, even failing to appear when Shredder and Krang returned for a story arc in the final season with no explanation for the bumbling duo's absence.
After the rights to Thomas the Tank Engine were acquired by HIT Entertainment, and some of the original producers left the show, several semi-regular characters, such as Duck, Oliver, Boco and Daisy, were dropped in order to focus on the Steam Team. This also happened to several one-off and recurring original characters that were made as an excuse to make and sell more toys. Season 17 and onwards however, seems to be slowly reinstating them back into the series after Andrew Brenner took over as head writer, with Duck, Bill & Ben, and Harvey re-appearing in season 17 in prominent and respectable roles, Oliver and Toad in season 18, and Daisy and Donald & Douglas in Sodor's Legends of the Lost Treasure; fans are hoping for the return of other favorite and Dark Horse Ensemble characters such as Arthur, Murdoch, Hank, Derek, Neville, Molly, and Duke. This trope can now be said to apply to the Logging Locos, whose main entrance way into Sodor was purportedly seen boarded up in several episodes without any explanation. Word of God later confirmed the tunnel wasn't boarded up, yet the Logging Locos still have yet to make a re-appearance outside a single eighteenth season cameo by Ferdinand and several learning segments, and they might as well remain gone since they were universally-panned for their one-note personalities, reckless actions, Ferdinand's grating catchphrase of "That's right!", Bash & Dash having very annoying voices and being redesigned in a way that their basis wouldn't be able to function, living on an island that is a veritable death trap, and, for many American fans, being offensive redneck stereotypes who just sit around, laugh, tell bad jokes, and see the obvious safety violations of Misty Island as "fun".
Though most of the characters from the movie made at the very least a cameo in the series once (even Scar did at one point under the name "Claudius"), Nala, the other lionesses, and young Simba (surprisingly) weren't in a single episode of Timon & Pumbaa, though they did return in the sequels.
Over time, several characters from the first and second seasons stop appearing after the movie and later seasons in order to focus more on the new characters. Having Loads and Loads of Characters in a Merchandise-Driven show, it's easy to forget and lose track on who's who. This meant characters who actually survived the film, such as Grapple, Sunstreaker, Hound, Jazz, and Cliffjumper, disappeared into thin air and reappeared in the realm of fanfiction forever. Put simply, if your toy wasn't on the shelves at the time (or was relegated to being a mail-away offer) you were liable to simply cease to exist without a word.
There is a bit of an explanation behind Jazz and Cliffjumper, though: Jazz's voice actor, Scatman Crothers, died shortly before the film was released, and Cliffjumper's voice actor, Casey Kasem, left the show due to disgust over the fictional nation of Carbombya (Kasem was of Lebanese descent).
Subverted in the case of several characters; Optimus Prime, Ironhide, Ratchet, Prowl, Wheeljack, Brawn (disputed), Windcharger, Huffer (offscreen), and Starscream were outright killed off in the movie. Megatron, Thundercracker, Skywarp, and the Insecticons didn't die, per se, but became new characters. And of course, Starscream came back as a ghost in season three (as his toy was still on shelves), and the collective outcry of the fanbase brought Optimus Prime back to life, even though he wouldn't have another toy until 1988.
The third season was even more confusing to Japanese viewers, because Transformers: The Movie wasn't released in Japan until 1989 (by comparison, it was released in the United States and Europe in 1986). This meant that characters who died in the movie such as Prowl and Wheeljack were alive and well in the Japanese-exclusive series.note Or they did die and were replaced by alternate selves from another universe, as described in various Japanese sources... yeah, it's complicated.
Other dead characters such as Huffer, Brawn, and Windcharger also appeared via animation errors in the third season, though Brawn's death is (jokingly) disputed in the fanbase, meaning he may not have died and his appearance in "Carnage in C-Minor" wasn't an accident; those who are serious about his survival note that Brawn was felled by a shoulder wound, when he survived two pointblank headshots from Megatron in the first season of the cartoon (in one episode, even), and was well-known for his tough armor. Then you have characters whose deaths were scripted, but never animated (such as Trailbreaker, Smokescreen, Red Alert, and Shockwave), making it ambiguous if they too survived or not.
Mary Jane mysteriously disappeared after Season 2. She finally came back in season four as the Carnage Queen.
J. Jonah Jameson. So far, he's been completely absent from season four.
This may be the fate of Vehicle Voltron in all Voltron shows post the original 1984 series. They don't get so much as a shoutout in either The Third Dimension or Voltron Force. Possibly it's a reflection of the lack of popularity of the Dairugger XV derived segment and World Events Productions reluctance to spend money retaining the rights to it.
The Wild Thornberrys had a pair of minor recurring villains named Kip O'Donnel and Neil Biederman, a pair of poachers who occasionally antagonized the titular family. While they were featured in the pilot episode, presumably to establish them as the main antagonists, they only made seven appearances in the main series before disappearing completely after the second season.
X-Men: Evolution: After the rise of Apocalypse, Sabretooth just disappears from the show. While its given a small Hand Wave courtesy of Pyro (claiming he was 'playing with a ball of yarn somewhere'), it's more of just Pyro rambling and doesn't mean a thing. Similarly, Destiny disapears in season 3 without any mention. When she last appeared she tells Mystique that she'll be involved in a plot to bring back an ancient mutant, but by Mystique's next appearence, she's working with Mesmero to bring back Apocalypse without any mention or reason.
The Lion Guard: Bizarrely, all of the lionesses in the pride have vanished except for Nala. They even added two female cubs that have no visible mother or father near by.