Two clownfish, Marlin and Coral, are admiring the view from their new home within a sea anemone overlooking the drop-off of a coral reef. The couple are waiting for their 400 eggs to hatch. Excited to be first-time parents, they discuss names, and Coral expresses her fondness for "Nemo". They flirt playfully with each other until Coral's attention is distracted by the appearance of a barracuda. Ignoring Marlin's order to hide, Coral rushes to protect the baby eggs encouraging the barracuda to attack. Marlin rushes in but the barracuda knocks him out with a flick of its tail, sending him back into the anemone. When he wakes up, he finds that Coral and all of the eggs have been eaten. All except for one, which has a little crack in it. Marlin vows to keep his only surviving child safe, and names him Nemo.
Nemo is born with a deformed fin due to damage his egg took. Marlin raises Nemo in a secure anemone further into the reef, and becomes overprotective of him. On the morning of his first day of school, an excited Nemo wakes his father. Marlin escorts Nemo to school while Nemo asks him many questions of the sea, to which Marlin is too reluctant and inexperienced to answer. At school, Nemo meets a seahorse named Sheldon, an octopus named Pearl and a butterflyfish named Tad. Their teacher, Mr. Ray takes them on a field trip to the drop off. When Marlin finds out about this, he follows after them in fear.
Upon arriving at the drop off, Nemo and his three friends wander off to the edge of the reef, where they see a boat in the distance. They take turns seeing who can swim closest to it, but Marlin arrives and yells at Nemo for endangering himself. Marlin decides Nemo isn't ready for school and tells him just because he thinks he can do something doesn't mean he can. Nemo tells Marlin he hates him, then swims all the way out to the boat to touch it. As he swims back, he gets captured by a scuba diver. Marlin tries to save him, but is temporarily blinded by a second scuba diver taking a picture of him. The diver places Nemo in a cooler full of water and accidentally pushes his mask into the water.
Marlin swims after the boat but eventually loses the trail. Asking for directions, he meets Dory, a blue tang with short term memory loss who offers to help. The two of them run into a great white shark named Bruce, who invites them to a get-together in a sunken submarine surrounded by live sea mines, despite Marlin's objections. They meet Bruce's fellow sharks, Anchor and Chum, before beginning an assembly where they pledge to abstain from eating fish. Marlin notices the diver's mask on the submarine. He accidentally hits Dory in the nose with it, giving her a nosebleed. The smell of blood excites Bruce and he chases Marlin and Dory through the submarine. During this time, Dory reveals that she can read human words. Bruce and the other sharks swim away when a torpedo from the submarine sets off all of the sea mines.
Meanwhile, Nemo has been placed in a fishtank in a dentist office in Sydney, Australia. He meets the "Tank Gang" consisting of Bloat the puffer fish, Bubbles the yellow tang, Peach the sea star, Gurgle the royal gramma, Jacques the cleaner shrimp, and Deb, a black-tailed humbug who believes her reflection to be her twin sister, Flo. Their leader is Gill, a Moorish idol with scars on his right side and who, like Nemo, came from the ocean. They are friends with a pelican named Nigel. Nemo discovers he's going to be given as a present to the dentist's niece Darla, who has a habit of killing her pet fishes, in a few days. Afraid and wanting to go home, Nemo gets stuck in the suction tube of the filter. Gill tells Nemo that he must escape himself, giving Nemo instructions and encouragement. Nemo manages to free himself.
Marlin and Dory wake up, but the mask falls into a deep dark trench. Descending after the mask, they are soon pursued by an anglerfish. Dory reads the address on the mask- "P Sherman, 42 Wallaby Way, Sydney"- and is ecstatic that she can remember it.
In the fish tank that night, the other fish perform an initiation to include Nemo in their club, giving him the nickname "Shark Bait". Gill then proposes a plan to escape the fish tank by having Nemo block the filter with a pebble, which would cause the tank to become so dirty that Sherman will have to manually clean it and place the fish in baggies on the counter, allowing them to roll out the window to the street, cross it, and land in the harbor. Nemo attempts to block the filter, but initially fails and almost ends up dying.
Marlin and Dory continue their journey and request directions to Sydney from a school of moonfish. They tell Marlin and Dory to take the East Australian Current (EAC). As Marlin swims ahead, the moonfish tell Dory that when they come across a trench, they swim through it and not over it. Marlin disregards these directions, and they go over the trench, where they end up surrounded by jellyfish. Luckily, the tops of the jellyfish don't sting, so they treat it like a game. But Dory fails to get out, having been stung repeatedly. Marlin, being more used to stinging sensations due to living in an anemone, manages to get her out before passing out. They wake up riding the EAC, helped out by a sea turtle named Crush and his son Squirt.
Marlin tells his story of how he's been travelling across the ocean looking for his son, and the story makes its way all across the ocean to Nigel, who tells the Tank Gang. Impressed by his father's bravery, Nemo tries to place the pebble in the filter again, and this time succeeds. The tank becomes covered in green algae.
Marlin and Dory continue along the EAC until they come to their exit point where Crush and Squirt show them where to depart the main line. Thanking Crush, Marlin asks the turtle how old he is, since one of the questions Nemo asked him is how was old sea turtles are. Crush answers that he is 150 years old and still young. Marlin and Dory get consumed by a blue whale, who expels them through its blowhole into Sydney Harbor.
The Tank Gang wake up to find the tank is completely clean after Sherman installed a laser filter, thus ruining their escape plan. Sherman suddenly pulls Nemo up in a fishnet but Gill and the other fish swim into it and instruct Nemo to swim down, pulling the net into the tank and away from Sherman's grip. Despite their efforts, Nemo is quickly scooped up in a plastic bag and set on the counter. The other fish tell Nemo to roll out the window but, before he can get far, Sherman places the baggie in a tin to keep him from moving. Gill tries to assure Nemo that he'll be okay but, at that moment, Darla crashes into the office.
Marlin and Dory meet Nigel, who takes them to Sherman's office after escaping a flock of seagulls. Nemo plays dead in the hopes Sherman will flush him down the toilet, but instead is going to put him in the trash. Marlin forces Nigel into the office and assumes Nemo is dead when he sees him. Sherman throws out Nigel along with Marlin and Dory. Gill uses the fishtank's volcano to launch himself out of the tank. He lands on Darla's head, and she drops Nemo's bag on a table full of tools, breaking the plastic. Gill catapults Nemo into the sink, as all drains lead to the ocean. Sherman quickly puts Gill back into the tank where he can breathe.
A depressed Marlin bids farewell to Nigel and Dory and begins his journey home. Nemo meets Dory, but she does not remember him until her memory returns when she reads the word "Sydney" on a drainpipe. Nemo and Marlin reunite, but a fishing trawler captures several fish in a net, including Dory. With his father's blessing, Nemo enters the net, and he and Marlin instruct the fish to swim down. Their combined forces break the net and free the fish. Nemo takes back saying that he hates Marlin, and Marlin tells Nemo he met a 150-year-old sea turtle.
The three of them return home to the reef, and Marlin has become more upbeat and confident in his son's abilities. Dory has remained friends with Bruce, Anchor, and Chum. Nemo hugs his father before heading off on another field trip with Mr. Ray. Marlin watches them leave, knowing that his son will be alright. Back at the dentist's office, Sherman complains that the laser filter broke, and he had to put the fish in bags. The fish successfully escape into Sydney Harbour before Bloat asks "Now what?"
