Genealogy of the Holy War, if the player pairs them: Tailtiu and either Azelle or Lex, Ayra and Chulainn, Erinys and Lewyn, Seliph and either Lana or Larcei, Lana and Ulster (and probably Diarmuid). Since the majority of the second-generation playable characters grew up together, it's kind of inevitable.
Thracia 776: Leif and Nanna, raised together by Nanna's father Finn and later living with Lana's amnesiac aunt Eyvel.
The Binding Blade: Lilina, if paired with Roy. Also implied with Zeiss and Ellen, though in this game only Roy will get paired endings.
The Sacred Stones: Tana if paired with Ephraim, Innes if paired with Eirika, Colm and Neimi, Artur and Lute, Kyle if paired with Syrene. And no matter who Eirika is with, Lyon will end up as a specially tragic Unlucky Childhood Friend.
Fire Emblem Awakening: Two of Chrom's potential wives are Sully (Childhood playmates and fellow soldiers) and Maribelle (noblewoman from a family close to his own, best friend of his younger sister Lissa), so it can go both ways.
In the case of the Second Generation children, they've all known each other from childhood due to their parents being Chrom's friends, retainers and partners. In several instances, the involved parties confess the sparks have been there since they were introduced to one another. The most obvious cases involve Sumia's daughter Cynthia and either: Olivia's son Inigo (she has liked him from a while already), Lissa's son Owain (who says he has always had a crush on her), or Cherche's son Gerome (whom she helped get over his former fear of heights when they were kids, and who may or may not have liked her from then on).
Also Chrom's daughter Lucina and any of her suitors save the Male Avatar, but especially the aforementioned Gerome. Right before their mutual Love Confession, she calls him her "most stalwart companion ever since childhood."
Owain himself can be caught by surprise by Cordelia's daughter Severa, who reveals that she's been enamored with the boy for a long time because of his unwavering kindness to her, even going as far as to inscribe his name on her weapon. Severa also can tell Maribelle's son Brady that she roped him into her wacky schemes involving the S&B note Snark & Bark Society simply so that they could spend some time together, just the two of them. And speaking of Brady, he and Tharja's daughter Noire end up kindling a romance when, repeatedly ending up as cot mates in their camp's healer's tent (she's anemic, he has the physical constitution of a paper bag), they reminisce about "the good old days" where they constantly traded illnesses back and forth and both vow to get stronger so they can help out their friends on the battlefield. And speaking of Noire, she can reveal she's been crushing on Inigo due to being the only girl he doesn't hit on (he hasgood reasonsfor that)... If it wasn't clear already, the game is just rife with this.
The Female Avatar can pull this with her Forgotten Childhood Friend Silas or with Jakob, her Battle Butler ever since they were children. The Male Avatar has either Felicia or Flora as candidates for this trope too, since they've been his ninja maids from childhood.
On the Hoshido side, Prince Takumi and his little sister Sakura's best friend Hana used to train together. The same goes to Takumi's older sister Hinoka and Hana's partner Subaki, who actually was her Big Brother Mentor. And it also turns out that a retainer of Takumi and Hinoka's eldest brother Ryoma (Saizo) and one of their mother Mikoto (Orochi) met as pre-teens. Therefore, this trope takes place if either of these duos hook up.
Among the Second Gens, where the localization downplayed some of their romances in favor of Just Friends-like interactions (and some romantic rejections), the most blatant examples would be Female Kana and Kiragi (who make a Childhood Marriage Promise) and Male Kana and Selkie. Though it's all but stated that Male Kana will eventually hook up with either Nina, Rhajat or Mitama, shall he reach an S Support with either of them, and Female Kana may also do the same if she has one with Prince Siegbert.
Potentially Aika and Vyse from Skies of Arcadia. The game's pretty vague about there even being a love triangle to resolve, though. Aika gives Vyse a kiss on the cheek, but Fina gets an arm around her in a scene either right after or right before.
The US release almost has a canon couple in the protagonist and Bianca, considering that the box art has two blond children (Flora and her children have blue hair). The Japanese DS release does this as well, but it's less obvious since the blonde children are on the back cover rather than the front.
Official art always shows the children with blonde hair, and every version of the game to date has featured Bianca on the front cover, and the back cover of the Japanaese DS release is the only time Flora has appeared in the box art at all. The creators really aren't subtle about the fact that they think Bianca is a co-main character and Flora...isn't.
The Hero and Medea in the true ending Dragon Quest VIII. There are game features that allow the Hero to talk with Medea (who is normally stuck as a horse) and they talk about both current events and their past together before the story started. It's even more awesome because they destroy an Arranged Marriage to an utter Jerkass, yet still fulfill the terms of the original promise.
The 3DS remake of the game however subverts this, allowing the hero to marry Jessica, a fellow party member.
Dragon Quest XI has Gemma, who the Luminary has the option of marrying in the post game. Much like the remake of VIII, the Switch port gives the player the option of marrying their party members instead, though she is still presented as the primary choice.
In Overlord II, Kelda is the childhood friend of the Creepy Child that is to become the Evil Overlord and the only Nordbergian to actually like him (despite allreason), resenting her hometown for tossing him out for the magic-hunting Glorious Empire. When he returns approximately thirteen years later to conquer Nordberg she quickly joins him as a Mistress, though she eventually has to share him with two other mistresses. She can still be this trope if the player keeps her as First Mistress.
The Legend of Dragoon: Dart and Shana briefly had a Like Brother and Sister thing because he was raised by her family. There's a flashback showing them as children playing together and Dart scaring away a feral dog to protect Shana. They hook up at the end of Disc 2 and are still a couple in the epilogue.
Final Fantasy IV presents a Love Triangle variant, with Cecil and Kain both having known Rosa from their younger days, and both had feelings for her. But she only had feelings for Cecil, which caused Kain to briefly betray Cecil out of jealousy. The three eventually reconciled, with Kain finally accepting his friends' relationship.
Final Fantasy VII: Cloud and Tifa have known each other since their days in Nibelheim, and she was the reason he eventually decided to join SOLDIER. Though Tifa didn't develop feelings for Cloud until after he'd left. During the events of the game they confess their feelings for each other and start a family in the compilation.
Irvine and Selphie in Final Fantasy VIII grew up together in an orphanage (along with Squall, Zell, Quistis and Seifer), but due to exposure to Guardian Force summons Selphie didn't remember him at first. Whether they ended up together or not is up to interpretation, but it is assumed that something is happening.
In Final Fantasy X, at first, it appeared that Wakka was an Unlucky Childhood Friend. He had known Lulu since they were kids, but she had fallen in love with his younger brother. When his little brother died, it appeared that Lulu wouldn't accept anyone else into her life. We see in the sequel, Final Fantasy X-2, that they are married and have a boy.
Vaan and Penelo in Final Fantasy XII, though you have to work really, really hard to see the scene where they kiss each other in the secret ending of Revenant Wings.
In Final Fantasy XV, Noctis and Lunafreya (called 'Luna' by Noctis) grew close as children when Luna kept him company while he recovered from a near-death experience. As young adults, they are betrothed to be wed in a political marriage, although Noctis is hesitant. By the end, it seems he's come to accept his feelings for her however.
Jade Empire has Dawn Star, the sweet-natured childhood friend of the Player Character. A male character has the option of flirting, and eventually pursuing a relationship, with her. Played with a bit in that despite the player character's flirting, she never actually twigs to the idea of their relationship being romantic until Silk Fox shows up and pronounces Dawn Star a rival for the player character's attentions. A female character can become Heterosexual Life-Partners with her instead.
In Kingdom Hearts, you have Sora and Kairi. They've been leaning there since day one. Finally made official in III, with them sharing a paopu fruit.
Siskier and Garlot in Blaze Union, but it only happens in the C route.
Gabriel and Marie Belmont in Castlevania: Lords of Shadow, who meet their tragic doom just before the beginning of the story; especially think about how sweet and warm it was when they married each other, fulfilling their promise to stay together forever. For such a reason, Gabriel breaks down completely after failing to resurrect her. Imagine how happy Gabriel must have been before Marie's tragic death...
The earlier Castlevania: Chronicles of Sorrow duology also heavily implied this regarding Soma Cruz and Mina Hakuba. In Dawn, it may end just as badly as Gabriel's situation did.
In Xenoblade, Shulk and Fiora seem to be going in this direction until Fiora is killed in the Mechon assault... but, then it turns out that she wasn't quite dead and they hook up in the ending.
In later games, Ichinose and Aki are implied to be in a Long-Distance Relationship. It's doubly meaningful since Aki used to be the unlucky variation to The Hero Mamoru Endou.
While the aforementioned Endou tends to marry his junior-high classmate Natsumi in the animes, mangas and the Shine versions of the GO game, in the Dark version of GO he can marry his childhood friend Fuyuka instead.
Guillo in Baten Kaitos Origins. Other obstacles standing between him/her and Sagi include the fact that he/she is a living puppet, and the fact that Sagi probably always thought of him/her as a man, even though he/she technically has no gender. Or rather he/she is both gender since he/she seems to be deeply influenced by his/her creators, who were a man and women and are the ones he/she got her voice(s) from.
Super Robot Wars Original Generation. Kushua Mizuha begins the game with a crush on her childhood friend Ryusei, but by the middle of the game, has moved on to somebody else. In the Alpha series, however, she does end up with her friend (who was not Ruysei), but since the first OG game came out between the first and second Alpha games, it wasn't quite a foregone conclusion until she appears in her Mech from Alpha 1.
The Disciple from Knights of the Old Republic II: The Sith Lords to a female player character who ends up with Atton or doesn't pursue a relationship might count. Canonically, the Disciple had a massive crush on the Exile from their first meeting when both were in their mid-teens, but the Exile was completely oblivious to his attraction and never really reciprocated.
If the Exile is chosen to be male, it is heavily implied, through dialogue with Kreia, that Jedi Master Atris had strong feelings for him. But the Exile never reciprocated these feelings either.
There's a sidequest early in Jade Empire that deals with this. You come across a woman who tells you that her husband is being menaced by a gang of bandits. You later come across the bandit leader....who turns out to be said Unlucky Childhood Friend for the husband.
The Unlucky Childhood Friend variant is a running theme in the World of Mana:
A childhood connection with the main winnable character is a staple of the Tokimeki Memorial series. Whether the player character chooses to pursue a romance is up to the player; whether or not they succeed is up to how well the player understands the game.
Possibly role-flipped in the first Tokimeki Memorial game: it is likely for the player character to become unlucky when pursuing childhood friend Shiori Fujisaki, as she is actually one of the harder girls to win over (due to high stat requirements across the board). If you play the game the right way, you'll be victorious instead. — except in Nijiiro no Seishun and Irodori no Love Song where Saki and Ayako are the respective heroines and main interest of the protagonist. all the other media treat the pairing as the Golden Ending, including the Motto! Tokimeki Memorial Radio Drama series,
And as of Tokimeki Memorial 4, because the Radio Drama-exclusive characters became Canon Immigrants in this game, and seeing the Ending of Shiori's Expy Yuu, it's strongly implied that the pairing is the 100% canon one in the main series:
This trope is also very important in the second game: The protagonist was childhood friends with several of the girls, but had to move away years ago and they were all heartbroken upon that. These ladies are: Hikari Hinomoto (main protagonist), Kasumi Asou, Akane Ichimonji, Homura Akai, Mei Iijyuin, Miho Shirayuki and Miyuki Kotobuki. It's specially bad in the case of Akane, since that is the actual reason why her super protective older brother Kaoru, the infamous Sou-Banchouhates the protagonist so much.
Back to Nature's version for boys is especially notable because it includes a backstory for the male player character in which he met a girl and played with her as children. This is an unusual case, however, because you learn this in a flashback and the flashback is deliberately designed to not make it clear who this is, since the little girl in the flashback has features that look like they could belong to any of the girls. And guess what? No matter which girl you romance, that girl will always turn out to have been whoever it was you played with as a little boy.
Chrono Cross clearly demonstrates this trope, with the male lead Serge already dating a girl called Leena, who later (rather unceremoniously and silently) gets shafted as Serge more or less begins to ignore her completely as the plot starts to thicken. Even if you put Leena in your party at every opportunity, she still gets no attention from her boyfriend! The main ending of the game even implies that Serge and Kid (the female lead) are destined to be together.
Of course, the Leena who joins your party isn't the same as the Leena that Serge was dating, thanks to that trip to an alternate dimension.
Shin Megami Tensei I begins with the player character Dreaming of Things to Come, including a specific woman... followed by his mother waking him up and mentioning he was yelling their neighbor's daughter's name in his sleep. Since The Hero is a Silent Protagonist, you only have other people's reactions to go by in interpreting their relationship, which can come out reading like he is an Unlucky Childhood Friend since it's soon revealed she has a new boyfriend. It turns into a plot-critical subversion because he was actually dreaming of the Heroine, who has the same name but is otherwise nothing like the neighbor girl.
All of the romance options in Persona 2: Innocent Sin are one of these, as the final party is composed of a group of childhood friends, even if most of them had forgotten about each other for a good decade or so, partially through trying to forget a traumatic separation and partially through the implied influence of supernatural forces.
In Persona 3 Portable, much of Rio Iwasaki's Social Link deals with her crush on her oblivious childhood friend Kenji Tomochika.
Eternal Sonata has Falsetto as the Unlucky Childhood Friend for Jazz whom seems to be in a relationship with Claves.
In Dragon Age: Origins, Tamlen from the origin for the Dalish Warden becomes an Unlucky Childhood Friend if said Warden is female. The female mage can also actually establish herself to be one — while Jowan is introducing her to his covert girlfriend Lily, she can state that she actually has feelings for him, and if she says she means it, he'll become flustered that she's bringing it up in front of Lily and exclaim that she's like a sister to him.
Adele is an one-sided example for L'Arc in Arc Rise Fantasia. She doesn't take it well.
The Lone Wanderer and Amata are implied to have feelings for each other in Fallout 3, something her father doesn't fancy the idea of. They never get together because depending on LW's actions in the quest Trouble on the Homefront, he's either thrown out of the Vault for good or she gets killed (either by the LW himself or a group of Enclave soldiers). On the other hand, the "best" resolution of the quest has Amata becoming the new Overseer and hinting at the possibility that she will accept the LW back in the future.
Mayor MacCready of Little Lamplight in Fallout 3 isn't necessarily friends with Lucy due to his abrasive personality, but they were certainly acquaintances and allies. By Fallout 4, they are married with a child until Lucy's death.
The incarnations of Link and Zelda from The Legend of Zelda: Skyward Sword are stated to have been very close for a long time prior to the game's events (their entire community is well aware, and one of whom, Groose, even harbors extreme jealousy over it) and there are hints of deeper feelings between the two, both in the game and in the marketing material. The end of the game doesn't state whether they choose to be a couple, but it does end with them choosing to stay together.
Link and Mipha in The Legend of Zelda: Breath of the Wild were close childhood friends before either was chosen as Champion of their respective races (and technically, Mipha is still a child by Zora standards by the time Link reaches adulthood). One line of dialogue between Mipha and Zelda implies the former always thinks of Link in order to use her healing magic, though she got interrupted by Ganon's return before she could finish. Mipha also crafted the Zora Armor specifically for the person she intended to marry, per Zora tradition, and it becomes a meaningful subject that it fits Link exactly when attempting to convince a Zora elder to allow Link to tackle Vah Ruta. Whether or not Link returns Mipha's feelings depends on a quick dialogue option with her father King Dorephan, and even then there's nothing else indicating how Link feels.
The Unlucky Childhood Friend variant is quite prominent in Ocarina of Time, as it was originally envisioned to have Dating Sim events and a lot of female acquaintances as a result. The Dating Sim was dropped, but the women were not, resulting in Link getting with none of them (granted, he's nine years old, and the Dating Sim was conceptualized before Child Link was). Truest to the trope is Saria, Link's Only Friend in his home village that he knew his whole life; rather than there be a possible case of First Girl Wins, she's the first girl he loses.
Dias and Rena from Star Ocean: The Second Story grew up together and have been close since childhood, until Dias suffered a tragic loss and decided to leave the town. The couple can go either way with this trope, depending on whether the player chooses to attempt to earn Rena's ending with Dias or pursue someone else. The obscure sequel establishes that they did not.
Takamizawa Natsuki is an Unlucky Childhood Friend example in Yoake Mae Yori Ruriiro Na and its anime adaptation, Yoake Mae Yori Ruriiro Na ~Crescent Love~.
RPG Shooter: Starwish has the protagonist Deuce work as a pirate with a crew. His childhood friend Tessa serves as the ship medic. Whether or not she is victorious depends on the player.
Mortimer and Bella Goth, a married couple in The Sims, are revealed to have been friends since childhood in the prequel, The Sims 3.
In general it's easier to do this than to have them meet as an adult, as relationships are hard to manage and it's much easier to have Sims date people they already know.
The main character in Queen's Tales: The Beast and the Nightingale has a childhood friend named Dorian who keeps sending her love letters despite the fact that she doesn't feel the same way.
Life Is Strange focuses primarily on the relationship between Max Caulfield and Chloe Price, two childhood friends who have become very different people in the 5 years of Max's absence. The nature of their intense friendship is left intentionally ambiguous for most of the game but, depending on player choices, becomes increasingly clearly romantic as the story progresses. Max's final journal entry is a reflection on Chloe's importance to her and whether Chloe returns her feelings. Word of God confirms the "Sacrifice Arcadia Bay" ending will result in this trope shortly after as the two girls recover.
The Excuse Plot in Hometown Story has the player move back to a village in which it lived during early childhood. When the mayor's son moves back in soon after the player, he reveals he and the player were childhood friends. If the player is female, he's also one of the villagers that she can marry.
Edge and Reimi in Star Ocean: The Last Hope develop one of these if you work on their relationship through the game. If you take it as far as possible, they'll share a kiss in their final Private Action before the final boss and their ending scene implies the two got married.
In any other game, Osana Najimi would be attempting this trope with her best friend, Taro/Taeko "Sempai" Yamada. Unfortunately, she's in Yandere Simulator, therefore has Ayano "Yandere-chan/Yan-chan" Aishi attempting to prevent this trope from happening by any means necessary.
In Lunar: The Silver Star, Alex and Luna were raised together by Alex's parents after Luna was left in their care as an infant, and by the start of the game are dating in all but name. They officially get together in the game's ending.
From the same game, Jessica and Kyle also grew up together and wind up as love interests. Unusually for this trope, they actually started dating before the start of the game, but have a NASTY breakup fight shortly before the heroes meet either of them (to the point where Kyle is in the process of getting as drunk as possible to get over her when the team first encounters him), only to both join the heroes and rekindle their relationship over the course of the game.
In Lunar: Eternal Blue, Ronfar is introduced as a womanizing gambler, but most of his character development comes from his past failure (and current desire) to save his childhood friend Mauri from becoming Brainwashed and Crazy by the Cult of Zophar (caused by a potion he gave her to cure a normally-fatal illness, which only furthered his feelings of guilt). He manages to break the curse, mostly by calling up his memory of making a Childhood Marriage Promise to her, and the two confess their love for each other. By the time Hiro visits them in the epilogue, at most a few months after Mauri is freed, they're living together, and Ronfar is happily a one-woman man.
Trillion: God of Destruction: Levia, the Overlord of Envy, was a childhood friend to Great Overlord Zeabolos prior to obtaining her position. (The PC version of the game has several short stories centering on the Overlords — hers shows how Zeabolos and she met.) If Levia is successful in killing Trillion and becoming the new Great Overlord, her Good Ending shows that she manages to fulfill this trope and gets married to Zeabolos.
In Front Mission 5, there's Walter Feng and Lynn Wennwright, who were childhood friends. It's also played with for a bit, in that Lynn was a Forgotten Childhood Friend, and they only hook up once Walter transfers out of her unit and the main plot is dealt with.