Dr. Jumba Jookiba is put on trial by the Galactic Federation for "illegal genetic experimentation"—the evidence of this is Experiment 626: an aggressive creature that is nearly indestructible and learns quickly. Jumba is imprisoned while Experiment 626 is to be exiled on a desert asteroid. During transport on Captain Gantu's ship, 626 manages to break out of his cell and cut off the ship's power grid. 626 hijacks a police cruiser unit upon his escape, but finds himself outnumbered and outgunned. Surrounded, 626 activates the hyperdrive and breaks through their defense, setting coordinates at random, landing him on the planet Earth. The Grand Councilwoman orders Jumba to work with Agent Pleakley to recover 626 discreetly. 626 survives his escape attempt to Earth, landing on the Hawaiian island of Kauai (Okina), but is knocked unconscious by a passing truck, and is taken to an animal shelter because he is believed by the truck drivers to be a breed of dog.After the recent death of their parents in a car accident, Nani Pelekai is looking after her younger, more rambunctious sister, Lilo. They are visited by Cobra Bubbles, a social worker, who is concerned that Nani can not take adequate care of Lilo. He considers putting Lilo into foster care, but Nani does not approve, as Lilo and she are the only remaining members of her family; Lilo does not help as she does not understand what may happen. After hearing Lilo in her room pray to be given a friend (Lilo has no real friends because every girl in her class makes fun of her), Nani agrees to allow Lilo to adopt a dog. At the shelter, Lilo immediately takes a keen interest in Experiment 626, despite serious misgivings that Nani and the shelter worker have about him being a dog. Lilo names 626 Stitch and shows him around Hawaii; Stitch quickly discovers escape is impossible due to the island being surrounded by water (his body is too dense for swimming) and that there are no large cities, which Jumba had previously said he would seek out to cause chaos, and suffers a nervous breakdown.As Nani attempts to find a good job, after being fired because of Lilo and Stitch, she is forced to bring them with her. Lilo uses the time to try to curb Stitch's aggressiveness by encouraging him to behave like Elvis Presley, whom she calls a model citizen as well as reading the book The Ugly Duckling to him. Stitch's antics, although at times foiling Jumba and Pleakley's attempts to capture him, also ruin Nani's chances of getting a job. David, a friend of Nani's, sees her at the beach, where she was trying to get a job as a lifeguard. David suggests they go surfing to improve her mood. While Nani, Lilo and a panicking Stitch ride on a huge wave, Jumba makes one more effort to capture Stitch from underwater; as a result, it appears as if Stitch attempted to drown Lilo. Although everyone gets safely to shore, Cobra saw the whole thing and tells Nani he will come by in the morning to take Lilo away from her and leaves feeling sorry for her. After Stitch sees how much trouble he has caused, he leaves, taking the ugly duckling book with him in hopes of finding his "family".The next morning, as Nani waits for Cobra to arrive, David tells Nani of a job offer that she must respond to. Nani tells Lilo to stay at home while she goes to secure the job. Stitch, hiding in the nearby woods, encounters Jumba, who reveals that Stitch can never have a family or "belong" because he was just built to destroy. Stitch races to Lilo's house, followed by Jumba firing at Stitch with his gun. The two fight, with Lilo immediately phoning Cobra for help. The house is ultimately destroyed by the end of the fight, with Nani and Cobra arriving shortly after. As Nani and Cobra argue over Lilo's well-being, Lilo slips away to hide in the forest and finds Stitch, who reveals his true alien identity form to her. While she says how he ruined everything, they are both captured by Captain Gantu, who had been sent to capture Stitch after Jumba and Pleakley failed to do so, and he makes to leave Earth. Nani is shocked to see Gantu putting Lilo and Stitch in a container pod and taking off in the ship. Stitch escapes from the container before the ship takes off, leaving Lilo behind. Nani then realizes that Stitch isn't what she thought he was, and demands he had better speak, just as Lilo always said he did.While once again trying to capture Stitch, both Jumba and Pleakley are revealed to Nani, and tell her that they do know Lilo, and they can both get her back. Stitch, with help from Jumba's ship and by launching a gas tanker truck out of a volcano, is able to free Lilo and stop Gantu. After they land, they find that the Grand Councilwoman has arrived nearby, in order to capture Stitch personally. When she sees Stitch has developed a sense of respect and compassion, she realizes he has become a civilized creature and no longer an abomination. Using Lilo's certificate of Stitch's ownership, which proves that taking Stitch would mean stealing him from Lilo, the Councilwoman asserts that Stitch, now a part of Nani and Lilo's family, will live his exile on Earth with the humans as his warders. As her guards take Gantu away, she doesn't let Pleakley or Jumba return on her ship, and orders Cobra, a former CIA agent who previously met the Councilwoman at Roswell, to keep an eye on the new family. Stitch, Jumba and Pleakley become integrated into Lilo's family, and the house is rebuilt with the help of the three, David and Cobra.
- Littlefoot and the Land Before gang, Thomas the tank engine, Percy, James, Toby, Emily, Gordon, Henry, Edward, The Logging Locos (Bash, Dash and Ferdinand), Luke, Hiro, Charlie, Paxton, Victor, Kevin, Stanley, Rosie, Twilight Sparkle, Pinkie Pie, Rarity, Applejack, Rainbow Dash, Fluttershy, Spike, The Cutie Mark Crusaders (Apple Bloom, Sweetie Belle and Scootaloo), Shining Armor, Princess Cadence, Heckle and Jeckle, Sophie, Sky, Cool McCool, Bloom, Ash Ketchum, Pikachu, Misty, Brock, Togepi, Simba, Nala, Timon, Pumbaa, Zazu, Alex, Marty, Melman, Gloria, The Penguins of Madagascar (Skipper, Kolwalski, Rico, and Private), King Julien, Maurice, Mort, Terk, Tantor, Louis, Ray, Aladdin, Princess Jasmine, Abu, Genie, Iago, Sebastian, Baloo, Bagheera, King Louie, The Vultures (Buzzie, Flaps, Dizzy, and Ziggy), Jiminy Cricket, Kronk, Fu Dog, Kenai, Koda, Rutt and Tuke, Roger Rabbit, Littlefoot, Cera, Ducky, Petrie, Spike, Chomper, Ruby, Guido, SpongeBob SquarePants, Patrick Star, Squidward Tentacles, Sandy Cheeks, Eugene Krabs, Bloom, Stella, Musa, Tecna, Flora, Layla, Kim Possible, Ron Stoppable, Rufus, Mickey Mouse, Donald Duck, Goofy, Bugs Bunny, Daffy Duck, Scooby-Doo, Shaggy Rogers, Fred Jones, Daphne Blake, Velma Dinkley, Jean-Bob, Speed, Puffin, Devon and Cornwall, Mushu, Danny Phantom, Sam Manson, Tucker Foley, Jazz Fenton, Yogi Bear, Boo-Boo Bear, Snagglepuss, Huckleberry Hound, Quick Draw McGraw, Augie Doggie and Doggie Daddy, Wally Gator, Magilla Gorilla, Top Cat, Peter Potamus, Gwen, Kids World's Adventures Team and the characters will guest star in this film.