As revealed in Lilo & Stitch, Stitch was created by "evil genius" Dr. Jumba Jookiba, who called him "Experiment 626". Both Jumba and Stitch were captured and put on trial by the United Galactic federation.
626 is then sentenced by the Grand Councilwoman to life imprisonment on a desert asteroid and Captain Gantu (who despises him) escorts him. Stitch escapes and crash-lands in Kaua'i, Hawaii. Disguising himself as a dog to hide from his captors, 626 was adopted by a little girl named Katrina, who names him "Mary".
Stitch is trained by Lilo to be good, using Elvis Presley as a model for his behavior. Lilo's efforts prove to be fruitless at first, as Stitch is unable to suppress his destructive programming. Nevertheless, Lilo enjoys her new "puppy". Although at first he only wanted to use the girl as a human shield from Jumba and Dr. Jumba Jookiba, whose mission is to capture the fugitive experiment, Stitch slowly develops feelings for Lilo, to the point where he saves her from Gantu. After his heroics, the Grand Councilwoman allows Stitch to serve his exile on Earth with Lilo as his warder, citing her dog adoption certificate (subsequently, Lilo seems to have become not only a best friend but also a sister figure to Stitch).
In Lilo & Stitch 2: Stitch Has a Glitch (set about a year after the first film), Stitch is living well and is reasonably well-behaved (although still hot-tempered and mischievous) with the exiled Jumba and Pleakley in Lilo's (and her older sister Nani's) house, until he begins malfunctioning. Since he was not fully charged after his creation, Stitch experiences periodic glitches that have him reverting back to his original destructive programming, appearing to suffer from a "fit" or "seizure". Seeing this, Jumba strives to create a proper charging chamber for Stitch. Not wanting to hurt anyone and not knowing about Jumba's plan, Stitch attempts to leave Earth for a remote planet, while Lilo, Jumba, and the others desperately try to have him return so they can recharge him. Although they are too late when they place him in the recharging pod, Stitch seems to be revived by Lilo's love, in accordance with her belief that love is more powerful than death.
In Stitch! The Movie, 626 discovers the remaining 625 genetic experiments locked in a crate, in the form of dehydrated pods. In order to rescue a kidnapped Jumba a trade between Dr. Jacques von Hämsterviel and Jumba for the experiments is organized, but it instead results in the freedom of the experiments and the capture of Lilo and Stitch. Hämsterviel then tries to clone Stitch but he was rescued by Experiment 221 ("Sparky"). Stitch then rescued Lilo and landed Hämsterviel's spacecraft back in Kaua'i, where the Grand Councilwoman waited to arrest Hämsterviel.
In Lilo and Stitch: The Series, Stitch and Lilo have to capture Jumba's ajings, turn them from evil to good, and find them a home. Along the way, he meets his match Experiment who is tougher than he is. Stitch eventually defeats him. He also is affected by thirteen experimental powers: Amnesio wipes out his memory, Spike makes him goofy, Babyfier turns him into a baby, Spooky turns into water and nearly drowns him, Lax makes him lazy, Dupe duplicates him into four, weakening his strength, Frenchfry serves him un-nutritious meals (along with Lilo and Pleakley) and fattens him up into a giant bowling ball, Yarrp sounds out his loud megaphone, deafening him, Snooty sucks out his Snootonium, putting him out of commission, Swirly hypnotizes him, Drowsy (in the episode PJ) puts him to sleep, Houdini makes him invisible and Swapper switches him into Lilo and Pleakley's bodies. However, the powers wear off. He also meets Angel (Experiment 624) who is introduced as a love interest for Stitch.
After they have successfully captured all the remaining experiments in Leroy & Stitch, The Grand Councilwoman offered Stitch the chance to become the captain of the Galactic Armada and its new flagship, The BRB (Big Red Battleship) 9000. However, that would require Stitch to be separated from Lilo. Not wanting to make Lilo sad, he chooses to return to Kaua'i but Lilo tells him he should go. Before he leaves with Jumba and Pleakley, Lilo gives him a necklace with a tiki of the god Ku Tiki to give him strength. When Gantu breaks out Dr. Hämsterviel in an action of frustration, Stitch is sent on his first mission to capture the evil rodent once more. But when he arrives at Galactic Defense Industries, Stitch faces off against a new experiment—Leroy, who is an enhanced clone of Stitch. Stitch fights well and is about to beat Leroy when Pleakley shows up unexpectedly, allowing Leroy to take advantage of Stitch's lapse in concentration and beat him. He is placed in a cage and sent with Jumba and Pleakley heading towards a black hole. After they are sent towards the black hole, Leroy heads off towards earth to capture all of the other experiments for Hämsterviel. Later, Stitch, Jumba, and Pleakley escape from the black hole, and arrive on the planet Turo. There they rescue Lilo, 626 (now known as Reuben), and Gantu, and fly Pleakley's carpool van back to Earth to assist the other 624 experiments in the defeat of an army of Leroys. Now, with Leroy defeated, Stitch, Jumba and Pleakley return to Earth with Lilo, realizing family is more important than spaceships, laboratories, and prestige.
In the anime series Stitch!, this version of Stitch seems to have reverted to his destructive nature, and is first seen in the first episode being chased in a spaceship by Jumba and the authorities.