Season 1
- In episode 2, when George and Harold are auditioning to be DJs for the school dance, Mr. Krupp stops them before they even start, saying, "Hold it, fellas. I'm afraid you're just too darn loud!"
- From the same episode, the robot helmets George and Harold wear when they crash the school dance are a blatant reference to Daft Punk.
- The way George and Harold crash the school dance is very reminiscent of the "Stand Out" scene in A Goofy Movie.
- In episode 5, after saving George and Harold from the T.P. Mummy, Mr. Ree says, "If you want to live, come with me."
- Later on, during Mr. Ree's flashback of his old job at T.E.R.D.S., there is a scene that parodies the tragic window barrier scene from Godzilla (2014).
- The "Paint-O-Rama" from episode 6 is an obvious Bob Ross parody.
- This gem from episode 7:Ms. Anthrope: …Your shark is gone.
Mr. Krupp: Oh, no… close the beach.
Ms. Anthrope: What bea—?
Mr. Krupp: CLOSE THE BEACH!!! - "I came here to prank and chew gum. And we're not allowed to chew gum."
- The "Krupp Brain Council" sequences in episode 9 seem to be a mixed reference of both 12 Angry Men and Inside Out. And when they return as regulars in Season 3, they become a three-way between the aforementioned films and Dr. Strangelove.
- In episode 12, after he realizes that George and Harold's impending expulsion is actually causing his hair to grow back, Mr. Krupp's Imagine Spot has him standing at the front of a boat with his arms spread open, while a VERY unamused Ms. Anthrope holds onto him.
- In the season 1 finale, upon discovering that Melvin switched his rule book with a decoy, Mr. Krupp cries out, "IT'S A COOKBOOK!"
- Also, the way in which Dr. Vil Endenemys' true identity is revealed in the Season 1 finale reminded quite a few fans of The Reveal in Harry Potter and the Chamber of Secrets.
Season 2
- In the Season 2 premier, Melvin builds a Combining Mecha. George notes he must have watched Voltron.
- In episode 2 of Season 2, the boys end up running from a giant boulder in a tropical jungle. Just like that one movie.
- During Melvinborg's presentation in episode 3, there is a segment that parodies the ever-iconic "I'm Just a Bill" song.
- Mr. Krupp’s rather creepy ventriloquist's dummy (that is heavily implied to be alive, if the ending of episode 3 is anything to go by) might be a reference to Slappy the Dummy from Goosebumps.
- The boys watch a parody of Stranger Things called "Screaming Things" in episode 5.
- In "The Shadowy Syndrome of the Sinister Splotch", when Captain Underpants is fighting the Venom Expy from Season 1 (now named "Splotch" by George and Harold), Splotch at one point yells, "THERE CAN BE ONLY ONE!" This also doubles as an Actor Allusion, since Splotch is voiced by none other than the Kurgan himself, Clancy Brown.
- In "The Trashy Tale of the Tumultuous Tubbadump", the boys end up flying on a giant garbage bag and sing a duet together as they ride across the sky. The chapter is appropriately titled Magic Garbage Ride.
- After the Melvins send the trash to another dimension, Harold admonishes them with a "You maniacs!"
- For the Season 2 Finale, the Tattle Trials along with the boys competing against their friends is inspired by The Hunger Games.
- There is also a character named "Fingers the Petty Thief Panther" who is loosely based on the Pink Panther.
- The second half of the finale is chalk full of these as well.
- One scene involves CU, the boys and the Melvins flying to escape from a living cave monster reminicent of the Exogorth from the Empire Strikes Back.
- George and CU also make reference to the Die Hard series.
- Throughout the episode, the Captain sings a made up song that's loosely inspired by 'Another Day of Sun' from La La Land.
Season 3
- The Melviathan from episode 5 of Season 3 bears a loose resemblance to the Kraken from Clash of the Titans (1981).
- The giant bird that stalks Other Sophie uses infrared vision to hunt her.
- It can be argued that Captain Ultrapants' design was loosely inspired by the Hulkbuster.
- In episode 6, Mr. Krupp's Imagine Spot, along with the final fate of the Salamangler, involve being adopted by a billionaire alongside his singing house staff.
- In the Blah Borelock episode, Melvin's electronic nerd hat flies past the Keebler Elves' treehouse.
- All throughout "The Ghastly Danger of the Ghost Dentist" , there are scenes that feature Krupp, Melvin, CU and the boys running through the forest in a shaky camera style that's reminiscent of The Blair Witch Project.
- Bo's solo performance is loosely based on The Texas Chainsaw Massacre.
- George and Harold pay homage to iconic horror narrator Vincent Price by dressing up in red robes and donning mustaches.
- When CU meets Gumbalina's ghost, he flat out says "I ain't a fightin' no ghost!"
- In "The Confounding Concoction of the Crooked Combotato", Erica's story uses an art style that's similar to the one used on Archer.
- Krupp's purple talking dune buggy in episode 12 is a modernized version of Speed Buggy.
- For the season 3 finale, Dressy and the others sing a parody of "We are the Champions".
Season 4
- The season 4 finale ends with everyone crashing landing on a planet where Melvins rule the world and use an aesthetic reminiscent of the Planet of the Apes.
Holiday Specials
- Much like "The Ghastly Danger of the Ghost Dentist", the Hack-O-Ween Special is riddled with horror themed references.
- In a past Halloween, George and Harold dressed up as mustached (zombie) plumbers (albeit orange and blue instead of red and green).
- Jessica has Other Sophie dress up as "Noiseless Nancy" who is a spoof of Dr. Hannibal Lecter.
- CU's O-Rama fight against the giant inflatable Hack-O-Ween kaijus uses ominous floating balloons throughout the scene (albeit orange instead of red).
- The same segment features CU being attacked while taking a shower.
- Creepily's house becomes sentient via Melvin's Animanitator 2000 near the climax and attacks the heroes. So you could say, it became a Monster House.
- In the "Mega Blissmas Christmas Special", the stop motion segments are based on the specials created by Rankin/Bass Productions.
- Santa's "Blissmas" appearance bears a strong resemblance to Hulk Hogan.