Breakfast of Champions tells the story of the events that lead up to the meeting of Kilgore Trout and Dwayne Hoover, the meeting itself, and the immediate aftermath. Trout is a struggling science fiction writer who, after their fateful meeting, becomes successful and wins a Nobel Prize; Hoover is a wealthy businessman who is going insane, sent over the brink by his encounter with Trout.
Trout, who believes himself to be completely unknown as a writer, receives an invitation to the Midland City arts festival, and Trout travels to Midland City. First he goes to New York City, where he is abducted and beaten up by the only anonymous, faceless characters in the book, who through the media gain the moniker "The Pluto Gang." He hitches a ride first with a truck driver whose truck says PYRAMID on its side, with whom he discusses everything from politics to sex to the destruction of the planet. Then he hops a ride with the only clearly happy character in the book, the driver of a Galaxie who works for himself as a traveling salesman.
Dwayne Hoover gets more and more insane as the book progresses. He terrifies his employee at the Pontiac agency, Harry LeSabre, by criticizing his clothes. LeSabre is afraid Hoover has discovered that he is a closet transexual. Then he gets in a fight with his mistress and secretary, Francine Pefko because he accuses her of asking him to buy her a Kentucky Fried Chicken franchise.
Trout and Hoover meet in the cocktail lounge of the new Holiday Inn, where Hoover's homosexual and estranged son, Bunny, plays the piano. When the bartender turns on the black lights and Trout's white shirt glows brilliantly, Hoover is entranced by it. He accosts Trout and reads his novel, Now It Can Be Told. The premise of the novel is that there is only one creature with free will in the universe (the reader of the novel) and everyone else is a robot. Hoover interprets its message as addressed to him from the Creator of the Universe, and goes on a violent rampage, injuring many people around him and ending up in a mental hospital.
In the Epilogue, Trout is released from the hospital with a partially severed finger (Hoover has bitten it off in his rampage), and is wandering back to the arts festival, which has unbeknownst to him been canceled. The narrator, who has become an interactive character in the universe of his own creation, watches Trout and then chases him down. He proves that he is the Creator of the Universe by sending Trout all around the world, through time and back. Then he returns to his own universe, presumably, through the "void," while Trout yells after him, "Make me young!"
Throughout Breakfast of Champions, the reader is introduced to many minor characters as if they are major characters; the narrator points out that he means to write about life, and in life, everyone is as important a character as everyone else. He believes that the problems of the world can be traced back to humans wanting to live as if they are in a story book; this allows rulers to waste the lives of thousands of "minor" characters, and encourages people to kill one another and themselves for the effect of a dramatic ending. The narrator himself is an important character, interacting with the characters he has created and resembling Vonnegut himself in many ways.
The reader is also provided with short summaries of the works of Kilgore Trout. Their plots often demonstrate themes of Breakfast of Champions itself, a technique that aligns Vonnegut as an author with Trout as an author. For instance, Plague on Wheels deals with the extinction of a race of automobile-people. When the idea of the automobile is brought to Earth, Earthlings use it to destroy their own planet; the destruction of Earth is a theme that features frequently in Breakfast of Champions. Another example is "This Means You," in which a small percentage of the inhabitants of Hawaii own all the land, and decide to enforce a No Trespassing rule. The rest of the citizens, who do not own the land, are forced to dangle from the strings of helium balloons rather than paddle offshore. This story thus explores the theme of overpopulation (also touched upon in Trout's story Gilgongo!) as well as that of ownership, both of which are prominent in Breakfast of Champions.