Choke follows Victor Mancini and his friend Denny through a few months of their lives with frequent flashbacks to the days when Victor was a child. He had grown up moving from one foster home to another, as his mother was found to be unfit to raise him. Several times throughout his childhood, his mother would kidnap him from his various foster parents, though every time they would eventually be caught, and he would again be remanded over to the governmental child welfare agency.
In the present day setting of the book, Victor is now a man in his mid-twenties who left medical school in order to find work to support his feeble mother who is now in a nursing home. He cannot afford the care that his mother is receiving so he resorts to being a con man. He consistently goes to various restaurants and purposely causes himself to choke midway through his meal, luring a "good Samaritan" into saving his life. He keeps a detailed list of everyone who saves him and sends them frequent letters about fictional bills he is unable to pay.
The people feel so sorry for him that they send him cards and letters asking him about how he's doing and even continue to send him money to help him with the bills. He works at a re-enactment museum set in colonial times, where most of the employees are drug-addicts or, in his friend Denny's case, a fellow recovering sex addict. Victor spends most of his time on the job guarding his friend Denny (who is constantly being caught with "contraband", items that don't correspond with the time period of the museum) in the stocks.
Victor first met Denny at a sexual addiction support group (he was there as a chronic masturbator), and they later applied together to the same job. Denny is later fired from the museum, and begins collecting stones from around the city to build his "dream home;" Palahniuk based this portion of the novel on the true story of Ferdinand Cheval.
While growing up, Victor's mother taught him numerous conspiracy theories and obscure medical facts which both confused and frightened him. This and his constant moves from one home to another have left Victor unable to form lasting and stable relationships with women. Victor, as a result, finds himself getting sexual gratification from women on a solely superficial level (using sex anonymous meetings to find many of his sexual partners). Later on, he starts talking to his mother again for the first time in years.
The narrative is episodic, and is presented out of chronological order, a style common to the author's books.