The story begins on the far-off planet of Turo, where slightly mad scientist Jumba is on trial for creating Experiment 626, a small but deceptively dangerous monster whose sole design is to destroy everything with which he comes into contact. After the galactic authorities tag Experiment 626 as a bio-weapon with no other emotion than anger, Jumba is found guilty and sentenced to life imprisonment, while 626 is to be exiled on a desolated asteroid. However, while being transported to a remote asteroid, Experiment 626 manages to escape his prison transport, steal the “red” spacecraft, uncontrollably leap into hyper-drive, and elude death by landing in Hawai'i and avoiding the one thing that could kill him, water.
After landing on the island of Kaua'i, Experiment 626 is run over by a series of trucks and ends up being mistaken for a stray dog and incarcerated at the local dog pound. Meanwhile, the other little troublemaker, Lilo, is creating havoc and giving her older sister, Nani, a hard time. Not only does Nani have a difficult time with Lilo, but we soon learn that their parents are dead and she is being pressured by social worker Cobra Bubbles to prove that Lilo is getting the best care possible. In an effort of trying to explain this to Lilo, both get into an argument, which finally leads to Nani hearing Lilo wishing for a friend. The next day, Nani takes Lilo to the dog pound. It's there that Lilo adopts and names the extraterrestrial "Stitch."
Now that Stitch has changed his appearance so as to look less menacing, he is still faced with Jumba and Pleakley trying to capture him and take him back to the Turo. This only causes more problems for both Lilo and Nani, but at the same time, Stitch finds himself feeling as if he has a family for the first time.