Addie Bundren, the wife of Anse Bundren and the mother of a poor southern family, is very ill, and is expected to die soon. Her oldest son, Cash, puts all of his carpentry skills into preparing her coffin, which he builds right in front of Addies bedroom window. Although Addies health is failing rapidly, two of her other sons, Darl and Jewel, leave town to make a delivery for the Bundrens neighbor, Vernon Tull, whose wife and two daughters have been tending to Addie. Shortly after Darl and Jewel leave, Addie dies. The youngest Bundren child, Vardaman, associates his mothers death with that of a fish he caught and cleaned earlier that day. With some help, Cash completes the coffin just before dawn. Vardaman is troubled by the fact that his mother is nailed shut inside a box, and while the others sleep, he bores holes in the lid, two of which go through his mothers face. Addie and Anses daughter, Dewey Dell, whose recent sexual liaisons with a local farmhand named Lafe have left her pregnant, is so overwhelmed by anxiety over her condition that she barely mourns her mothers death. A funeral service is held on the following day, where the women sing songs inside the Bundren house while the men stand outside on the porch talking to each other.
Darl, who narrates much of this first section, returns with Jewel a few days later, and the presence of buzzards over their house lets them know their mother is dead. On seeing this sign, Darl sardonically reassures Jewel, who is widely perceived as ungrateful and uncaring, that he can be sure his beloved horse is not dead. Addie has made Anse promise that she will be buried in the town of Jefferson, and though this request is a far more complicated proposition than burying her at home, Anses sense of obligation, combined with his desire to buy a set of false teeth, compels him to fulfill Addies dying wish. Cash, who has broken his leg on a job site, helps the family lift the unbalanced coffin, but it is Jewel who ends up manhandling it, almost single-handedly, into the wagon. Jewel refuses, however, to actually come in the wagon, and follows the rest of the family riding on his horse, which he bought when he was young by secretly working nights on a neighbors land.
On the first night of their journey, the Bundrens stay at the home of a generous local family, who regards the Bundrens mission with skepticism. Due to severe flooding, the main bridges leading over the local river have been flooded or washed away, and the Bundrens are forced to turn around and attempt a river-crossing over a makeshift ford. When a stray log upsets the wagon, the coffin is knocked out, Cashs broken leg is re-injured, and the team of mules drowns. Vernon Tull sees the wreck, and helps Jewel rescue the coffin and the wagon from the river. Together, the family members and Tull search the riverbed for Cashs tools.
Cora, Tulls wife, remembers Addies unchristian inclination to respect her son Jewel more than God. Addie herself, speaking either from her coffin or in a leap back in time to her deathbed, recalls events from her life: her loveless marriage to Anse; her affair with the local minister, Whitfield, which led to Jewels conception; and the birth of her various children. Whitfield recalls traveling to the Bundrens house to confess the affair to Anse, and his eventual decision not to say anything after all.
A horse doctor sets Cashs broken leg, while Cash faints from the pain without ever complaining. Anse is able to purchase a new team of mules by mortgaging his farm equipment, using money that he was saving for his false teeth and money that Cash was saving for a new gramophone, and trading in Jewels horse. The family continues on its way. In the town of Mottson, residents react with horror to the stench coming from the Bundren wagon. While the family is in town, Dewey Dell tries to buy a drug that will abort her unwanted pregnancy, but the pharmacist refuses to sell it to her, and advises marriage instead. With cement the family has purchased in town, Darl creates a makeshift cast for Cashs broken leg, which fits poorly and only increases Cashs pain. The Bundrens then spend the night at a local farm owned by a man named Gillespie. Darl, who has been skeptical of their mission for some time, burns down the Gillespie barn with the intention of incinerating the coffin and Addies rotting corpse. Jewel rescues the animals in the barn, then risks his life to drag out Addies coffin. Darl lies on his mothers coffin and cries.
The next day, the Bundrens arrive in Jefferson and bury Addie. Rather than face a lawsuit for Darls criminal barn burning, the Bundrens claim that Darl is insane, and give him to a pair of men who commit him to a Jackson mental institution. Dewey Dell tries again to buy an abortion drug at the local pharmacy, where a boy working behind the counter claims to be a doctor and tricks her into exchanging sexual services for what she soon realizes is not an actual abortion drug. The following morning, the children are greeted by their father, who sports a new set of false teeth and, with a mixture of shame and pride, introduces them to his new bride, a local woman he meets while borrowing shovels with which to bury Addie.