Home opens with a memory of two kid siblings in Lotus, Georgia, watching through grass, the burial of unknown black bodies by men alongside horses. In the present day, Frank Money, a war veteran, awakens in a mental hospital room, cuffed to the bed. He recalls receiving a letter warning him: "Come fast. She be dead if you tarry." He escapes barefoot from the hospital to an AME Zion Church. He meets Reverend John Locke and his wife, Jean, who let him stay for the night. Reverend Locke gives Frank money to buy a bus ticket to Portland.
Frank travels on trains from Portland to Chicago, recalling gruesome memories of the war and of an apartment life alongside his former lover, Lily. A train waiter directs Frank to a restaurant called Booker's where he makes friends with Billy Watson who leads him to his house to meet his family and stay the night. Sleeping at their family's house, Frank suffers from nightmares throughout the night and worries about the letter he has received from a woman named Sarah that warns him of the danger his younger sister, Cee, has found herself in. Billy takes Frank clothes shopping where they are subjected to a random search by the police as they exit the store. The police let them go after taking note of the Korean War medal Frank dons.
In Atlanta, Cee recalls the two siblings' childhood in Lotus, Georgia living under their grandfather and his wife, Lenore. Cee is disregarded by her step-grandmother who regards the terms of her birth (being born in the street) as "sinful". The children's parents both worked multiple jobs and the care of Cee was left to Frank, just four years older. After Frank leaves for the war, Cee meets Prince, a boy visiting from Atlanta. Prince advances after Cee and the two later marry He takes Cee back to Atlanta, where she later discovers that he only married her so as to attain the vehicle her family would lend to him.
Now abandoned by Prince and unaware of his whereabouts, Cee lives alone and works as a dishwasher. Cee does not wish to return home, so she visits her neighbor, Thelma, to look for another job. Thelma informs her of an available job working for a doctor and Cee travels to the doctor's house where she meets their house-keeper named Sarah Williams. She gets the job and is told by Sarah that Dr. Beau works as a scientist and performs experiments. The following weeks follows Cee working and living at the Scott's house as she comes to admire the work Dr. Beau does for women.
Lily works as a seamstress before the studio she works at gets shut down and she returns to work as a cleaning woman, where she meets Frank. The two come to live together in her apartment, but Lily grows dissatisfied with Frank's lack of goals. After Frank leaves, Lily comes across a purse full of coins and feels relief and motivation towards her dream of becoming a successful seamstress.
Back during the Korean War, Frank looks back upon his memory of a young Korean scavenging for food everyday near their garbage. She is later killed by Frank's relief guard after grabbing his crotch. Frank arrives at Dr. Beau's house where the doctor fires a gun at him, but the gun's chamber is empty. He finds Cee unconscious and bloody and a taxi takes the two siblings back home to Lotus. Frank calls upon the help of a Miss Ethel Fordham who hurries Cee into her home.
While Frank is not allowed to enter Miss Ethel's house, the women in the neighborhood all visit Cee to give their own remedies to help heal her. Cee is nursed back to health for the next two months, but Miss Ethel reveals that her body is now unable to have children. It is then revealed by Frank that it was not the relief guard that killed the Korean child, but him after the girl aroused him when she touched his crotch. Frank takes Cee to the field they hid in as children to dig up the man's body they witnessed be buried as kids. They place his bones in a quilt made by Cee to bury him in the woods under a sweet bay tree.
