Lena Grove, a pregnant teenager, has made her way to Mississippi in search of her baby’s father. She hitches a ride into the small town of Jefferson, which is home to a planing mill. One of the workers at the mill, Joe Christmas, is a brooding, racially ambiguous man who appeared suddenly at the mill one day in search of a job. After gaining employment, he was soon joined at the mill by another man named Joe Brown. The two formed a partnership, making and selling liquor illegally, and eventually quit their jobs.
Another of the mill workers, Byron Bunch, is intrigued and unsettled when Lena Grove suddenly appears at the mill one day. He tells the town’s disgraced former minister, Reverend Gail Hightower, of his efforts to care for the girl. Soon, Lena comes to realize that the man she seeks—her baby’s father, Lucas Burch—is really Joe Brown. Upon Lena’s arrival in town, Brown is being held in the town jail after the murder of a local woman, Joanna Burden, and the burning of her home. Joe Christmas, Miss Burden’s occasional lover, is the chief suspect.
The narrative then shifts to explore several of the characters’ pasts. As a young minister, Gail Hightower secures a church in Jefferson to feed his obsession with his grandfather, a Confederate cavalryman who was killed in the town during the Civil War. Hightower’s young wife is unfaithful and grapples with mental health problems. She eventually dies in a fall from the window of a Memphis hotel room where she is staying with another man. A scandal ensues, and the Jefferson parishioners turn on Hightower, who is forced to step down.
As a child, Joe Christmas is left on the steps of an orphanage. When the facility’s dietician mistakenly believes that Joe has overheard her having sex with a young doctor in her room, she worries she will lose her job. To eliminate this risk, she threatens to expose young Joe’s biracial background and thus have him transferred to an orphanage for black children. She discusses the plan with the orphanage’s janitor, who kidnaps Joe and takes him to Little Rock, where he is found and returned, only to be adopted two weeks later by a sternly religious man, Mr. McEachern, and his wife.
Joe’s new foster father subjects him to regular beatings. As Joe grows and enters puberty, he eventually crosses paths with Bobbie, a prostitute who works as a waitress in the nearby town. When Mr. McEachern catches his son at a dance with Bobbie, a fight erupts, and Joe kills his foster father by smashing a chair over his head. Abandoned by Bobbie and her cohorts, Joe embraces a life on the run and wanders for more than fifteen years, eventually making his way to Jefferson.
In Jefferson, Joe Christmas stays in the cabin on Joanna Burden’s property, and the two quickly become lovers. Their relationship is marked by passion, violence, and long periods in which they ignore each other. Miss Burden wants a child and claims to be pregnant, but Joe is strongly opposed to the idea. After a time, Joe Brown comes to live with Joe Christmas in his cabin. Miss Burden tries to help Joe Christmas financially, but her meddling only provokes his ire. One night, he savagely attacks and kills her with a razor after she tries to fire a pistol at him in an apparent attempt at a murder-suicide.
Miss Burden’s nephew in New Hampshire offers a $1,000 reward for the capture of his aunt’s killer. Search parties with bloodhounds comb the countryside for the fugitive Joe Christmas, who eludes capture for days, running to the point of hunger and exhaustion. Lena, meanwhile, moves into the cabin that the two Joes had shared in order to prepare for the birth of her baby; Byron Bunch stays in a tent nearby.
Joe Christmas is apprehended on the streets of nearby Mottstown. His biological maternal grandfather, Uncle Doc Hines, makes his way through the crowd to curse Joe and call for his death. When the officials from Jefferson arrive to take charge of the prisoner, Mrs. Hines breaks through the crowd as well, hoping to see the face of the grandson who her husband told her died as a child. The Hineses then take the train to Jefferson together.
Byron and the Hineses arrive at Hightower’s house and reveal that Joe Christmas’s father was a circus worker who tried to run off with the Hineses’ daughter before Uncle Doc shot and killed him. Eventually, Uncle Doc placed the baby in the orphanage in Memphis where he worked as a janitor. Byron wants Hightower to lie and claim that Joe Christmas was with him, at his house, on the night of Joanna Burden’s murder. Hightower becomes angry and asks them to leave.
Lena goes into labor, but by the time Byron arrives with the doctor, Hightower has already delivered the baby. Assisting in the delivery is Mrs. Hines, who mistakenly believes that Lena is her long-dead daughter, Milly, and that the newborn is her grandson, Joe Christmas. Byron arranges to have Joe Brown sent to Lena’s cabin; upon arriving, Brown is shocked to see Lena holding his newborn son, slips out a back window, and runs away. Byron sees Brown escape and tries to stop him, but the much larger man beats Byron soundly and escapes on a passing train. Joe Christmas, meanwhile, escapes from his captors as well, while he is being led across the town square. Before long, he is tracked down, shot, killed, and castrated in Hightower’s kitchen by a bounty hunter named Percy Grimm. Afterward, the aging Hightower muses on his past and prepares for his own death.
After a road trip, a local furniture mover near Jefferson recounts to his wife how he gave a ride to a curious couple—a woman with a newborn child accompanied by a man who was not the child’s father. The couple—Lena and Byron—was halfheartedly in search of the baby’s biological father, as the man drove them deeper into Tennessee.