Marlin and Coral, a clownfish couple who are waiting for their eggs to hatch, live on the edge of the Great Barrier Reef. After a barracuda knocks Marlin unconscious, Marlin awakens to find Coral and all but one of the eggs gone. Marlin names the surviving child Nemo and vows to keep him safe.
Years later, Marlin and Nemo live in a secluded sea anemone. Nemo is eager to start school and explore the outside world; however Marlin remains anxious and hyperprotective of his son. While dropping Nemo off at school, Marlin warns the teacher of Nemo's deformed pelvic fin. After discovering Nemo's class will be visiting the "drop-off", where the reef meets the open sea, Marlin panics and tries to withdraw Nemo from school. Nemo defiantly swims to a nearby speedboat to prove his independence and is captured by a pair of scuba divers.
Marlin frantically races after the boat, disappearing into the horizon. He meets Dory, a blue tang with short-term memory loss who offers to help him locate his son. The pair encounter Bruce, a great white shark who is part of a support group of sharks trying to abstain from eating fish. At the meeting, Marlin finds a diver's mask from the boat with an address written on it. When Marlin accidentally injures Dory, Bruce smells her blood and relapses into a rampage that sets off old naval mines. As they escape, Dory recalls that she can read the address.
Meanwhile, Nemo is placed in a fish tank in dentist Philip Sherman's office in Sydney. He meets the "Tank Gang", led by Gill, a scarred Moorish idol and consisting of Peach the Sea Star, Deb the striped damselfish, Gurgle the royal gramma, Bloat the pufferfish, Bubbles the yellow tang, and Jacques the cleaner shrimp. They inform him that Sherman plans to gift Nemo to his hyperactive niece, Darla, who has an infamous history of killing her pet fish. To prevent this, Gill hatches an escape plan: Nemo, the smallest of the gang, will clog the tank's filter, forcing Sherman to clean it and bag the fish. Then, they can roll their bags out of the window and into the harbour. Nemo attempts the plan but is nearly killed by the filter's machinery in the process, causing Gill to feel deeply regretful.
Dory accidentally drops the mask into an abyss and encourages Marlin to help her search for it. They find the mask but are attacked by an anglerfish. Dory exploits the anglerfish's light to read the address while Marlin traps the anglerfish with the mask. Their victory boosts Marlin's confidence and helps Dory remember the address. Marlin tries to continue his search without Dory until she convinces a school of moonfish to give them directions to the East Australian Current. On their way, Marlin and Dory become trapped in a forest of jellyfish. While trying to escape, they are both stung and fall unconscious.