As I Lay Dying is told in individual sections, so that the narration of the story shifts from one character to another. While most sections are narrated by members of the Bundren family, the few that are told by neighbors and other observers offer a glimpse of the family from an outsider's perspective. Each narrator — family members and outsiders alike — is believable but at the same time unreliable, forcing readers to decide for themselves what is reality and what is not.
As the novel begins, Addie Bundren lays dying in her bedroom while her son Cash builds her coffin. Addie's ineffectual husband, Anse, is arranging to have her buried in Jefferson, a town forty miles away, because Addie has requested this last wish. Anse's motivating reason to go to Jefferson, however, is to get fitted for new teeth and, if possible, find a new wife. Two other sons, Darl and Jewel, struggle both with their mother's death and their own mental health. Darl is perceptive and insightful but taunts others mercilessly, while Jewel knows how to express love and affection only through violence, because his mother sought violence when she conceived him during an affair with a preacher.
Daughter Dewey Dell, a simple young woman who is incapable of forming deep, logically sequenced thoughts, is pregnant and in a hurry to get to Jefferson for an abortion. The youngest child in the Bundren family, Vardaman, is either much younger than his siblings or is mentally retarded; throughout the novel, he confuses his mother with the fish he catches on the day she dies.
To adhere to Addie's wishes, the family travels the distance to Jefferson during a hot, wet spell in Mississippi, and throughout the journey, Addie's body proceeds to decay, while buzzards swirl menacingly overhead. When they discover that a bridge has washed out, the family must find a way to get Addie's coffin over the river, and the ensuing scenes are both tragic and comic.
When these events become too horrific for Darl and he comes to understands that his mother needs to be buried properly, he tries to burn his mother's body and coffin in a barn, an act for which he is declared mentally insane. His father, Anse, allows Darl to be sent to an insane asylum because he does not want to reimburse the family for their barn, which was destroyed by the fire. Jewel, meanwhile, saves his mother's body from the fire, just as he saved her coffin from the swollen river, thus fulfilling his mother's prophecy that Jewel would save her.