Marlin (voice of ALBERT BROOKS) and Coral (voice of ELIZABETH PERKINS) are happy parents-to-be of several hundred clown fish and have moved to a new undersea home. Yet, disaster strikes and Marlin is then left alone with only one egg that he vows to protect.
Sometime later, it's the first day of school for young Nemo (voice of ALEXANDER GOULD), and Marlin isn't happy to let him out of his sight. That's not only due to him being an over-protective dad, but also because Nemo has a smaller than normal fin that doesn't bother the youngster, but worries Marlin.
To prove his dad wrong about such matters, Nemo disobeys his orders and sets out in the direction of a human boat. To Marlin's horror, a human diver than captures Nemo and speeds away, leaving Marlin shocked and heartbroken. After accidentally but literally running into Dory (voice of ELLEN DeGENERES), an optimistic blue tang with short term memory loss, Marlin discovers one of the diver's masks and then sets out to track the address on it back to his boy.
Meanwhile, Nemo has ended up in an Australian dentist's office in an aquarium with the likes of Gill (voice of WILLEM DAFOE), Bloat (voice of BRAD GARRETT), Peach (voice of ALLISON JANNEY),
Gurgle (voice of AUSTIN PENDLETON), Bubbles (voice of STEPHEN ROOT), Jacques (voice of JOE RANFT) and Deb (voice of VICKI LEWIS) who believes that her reflection is her twin sister, Flo.
Nemo's appearance stimulates Gil's desire to try to escape again and he hatches an elaborate plan to do so. It's important that they succeed since Nemo is targeted as a gift to the dentist's 8-year-old niece, Darla, who has a penchant for killing fish.
As they plot and prepare for their escape, Marlin and Dory make their way across the sea. Along the way, they encounter various creatures, such as three sharks -- Bruce (voice of BARRY HUMPHRIES),
Anchor (voice of ERIC BANA) and Chum (voice of BRUCE SPENCE) - who are going through an AA type step program to stop eating fish; Nigel (voice of GEOFFREY RUSH) the pelican; and laidback "surfer" turtle Crush (ANDREW STANTON) and his son Squirt (voice of NICHOLAS BIRD). With time running out, Marlin hopes to find and rescue Nemo before it's too late.