The novel is a first-person narrative, a monologue by a young Jewish man, Alexander Portnoy, who is speaking to his psychoanalyst. He shares his struggles with his identity as a Jewish man in America, his sexual fantasies and frustrations, his complex relationship with his overbearing mother, and his experiences of guilt and shame. The book uses humor and frank language to explore themes of identity, sexuality, and the Jewish experience in America.

This novel tells the story of Seymour "Swede" Levov, a successful Jewish-American businessman and former high school athlete from Newark, New Jersey. Levov's happy and conventional upper middle class life is ruined by the domestic social and political turmoil of the 1960s during the presidency of Lyndon B. Johnson, which in the novel is seen through the eyes of the narrator, Nathan Zuckerman, a budding writer who idolizes the Levovs. The novel portrays the impact of this turmoil on Levov and his family, particularly his rebellious daughter who becomes involved in revolutionary political activities.