The episode begins with Tweenis 12, one day's brain flight from Earth, collapsing due to an attack by giant brains.
Meanwhile, there is a pet show on Earth. After hearing that the top prize is $500 and dog food, Bender and Zoidberg plan to enter to win. Leela and Nibbler also enter. After a series of tests, the Hypnotoad wins by hypnotizing the judges. Nibbler is crowned the "dumbest pet in show" while Bender and Zoidberg the "whooping terrier" win second prize, much to Bender's disappointment.
Later the Planet Express staff discovers an ominous trail of destroyed planets leading toward Earth. Nibbler begins gibbering excitedly and runs away. Tracking Nibbler to an alley, Leela is attacked by giant floating brains. Leela is rescued by Nibbler, who has donned a uniform and is piloting a tiny flying saucer. Nibbler and Leela leave New New York and fly away from Earth.
The next day, Fry discovers that all the citizens of New New York have been rendered stupid, except himself. Meanwhile, Nibbler begins communicating to Leela telepathically, and they travel to the planet Eternium, at the exact center of the universe. There, in the Hall of Forever (10 miles west of the exact center of the universe), the Nibblonian council tells Leela of the threat of the Brainspawn, the giant brains that have invaded Earth and are attempting to wipe out all thought in the universe. While the Nibblonians have been fighting them for billions of years--since the beginning of the universe--they are powerless against the Brainspawns' powers of stupidity; in fact, Fry is the only being in the universe immune to the Brainspawns' mental attack, and is the only one capable of combating them.
Leela arrives on Earth to tell Fry of his mission, and retains just enough intelligence to remember what it is. In a successful leap of logic, Fry seeks the leader of the brains at the New New York Public Library. There Fry discovers that thinking hurts the brains, but the brain leader traps Fry and Leela in a mental realm based on Moby-Dick. Fry and Leela pursue the giant brain through The Adventures of Tom Sawyer, and into Pride and Prejudice. Fry breaks free of the illusion, and attempts to attack the giant brain. Fry's efforts result in him being crushed to death by a bookcase, but this is then revealed to be an illusion based on a story Fry has quickly written, one riddled with "plot holes and spelling errors". In accordance with the story the giant brain leaves Earth for no "raisin" ("reason"), and the people of Earth regain their intelligence. Other than the Nibblonians, Fry is the only other being in the entire universe to have any recollection of the event; every time he tries to recount the story, no one believes him or really cares about what he has to say. Nibbler, meanwhile, returns to his undercover position observing Earth as Leela's adorable pet.