Richard Wright's Uncle Tom's Children is a work made up of six distinct parts that include a nonfiction introductory essay followed by five fictional stories.

"The Ethics of Jim Crow" describes Wright's own experiences growing up. The essay starts with his first encounter with racism, when his attempt to play a war game with white children turns ugly, and follows his experiences with the problems of being black in the South through his adolescence and adulthood. It describes his experience of prejudice at his first job. While working at an optical factory, his white fellow employees bully and eventually beat him for wanting to learn job skills that could allow him to advance. Wright also discusses suffering attacks by white youths and explores the many hypocrisies of white prejudice against blacks. These include black men being allowed to work around naked white prostitutes while having to pretend they do not exist. Whites have exploitative sex with black maids, and yet any sexual relations between a black man and a white woman, even a prostitute, is cause for castration or death. Wright also delves into the more subtle humiliations inherent in the Jim Crow system, such as being unable to say "thank you," to a white man, lest he take it as a statement of equality.

"Big Boy Leaves Home" tells the story of a black teenager and his friends who have an unfortunate encounter with some whites. Big Boy and his friends Lester, Buck and Bobo are swimming on white property when a white woman surprises them. She begins to call for help, and her fiancy, an army officer, begins shooting with his rifle, killing Lester and Buck. Big Boy grabs the rifle and shoots the man, and then he and Bobo run. Big Boy and his family plan for him to escape. He will hide out all night in a kiln on a hillside and catch a ride with a black truck driver to Chicago in the morning. However, while hiding in the kiln, Big Boy witnesses a mob tarring, feathering and burning alive his friend Bobo, who was coming to join him. Big Boy must kill a dog that sniffs him out and passes the rest of the night crouched in shock and fear. He then meets with the truck driver in the morning and escapes, the sole survivor of the four friends.

"Down by the Riverside" takes place during a major flood. Its main character, a farmer named Mann, must get his family to safety in the hills, but he does not have a boat. In addition, his wife, Lulu, has been in labor for several days but cannot deliver the baby. Mann must get her to a hospital. He has sent his cousin Bob to sell a donkey and use the money to buy a boat, but Bob returns with only fifteen dollars from the donkey and a stolen boat. Mann must take the boat through town to the hospital, even though Bob advises against this, since the boat is very recognizable. Rowing his family, including Lulu, Peewee, his son and Grannie, Lulu's mother, in this white boat, Mann calls for help at the first house he reaches. This house is the home of the boat's white owner, Heartfield, who immediately begins shooting. Mann, who has brought his gun, returns fire and kills the man, while the man's family witnesses the act from the windows of the house.

Mann rows on to the hospital but is too late; Lulu and the undelivered baby have died. Soldiers take away Grannie and Peewee to safety in the hills, and Mann is conscripted to work on the failing levee. However, the levee breaks, and Mann must return to the hospital, where he heroically smashes a hole in the ceiling, allowing the hospital to be evacuated. Mann and another black man, Brinkley, are told to rescue a family at the edge of town, who turn out to be the Heartfields. Inside the house, the boy recognizes Mann, who raises an ax to kill the child, but he is stopped when the house shifts in the rising floodwaters. Mann takes the boy, the boy's sister and his mother to dry land. There, Mann cannot find his family, and the white boy identifies Mann as the killer of his father. Soldiers lead Mann towards their camp. Thinking himself doomed, Mann runs, and the soldiers shoot him dead by the river's edge.

"Long Black Song" takes place on a solitary farm, where a young black woman, Sarah, waits for her husband, Silas, to return from selling his crop. She also has to take care of her baby, Ruth. Sarah has fantasies about another man, Tom, and is unsure if she loves Silas. A white salesman shows up as the sun goes down and tries to sell her a record player. They make conversation, and as she gets him some water, he attempts to seduce her. Initially protesting, she leads him to the bedroom, and they have sex. He leaves the record player with her and says he will try to return in the morning and convince her husband to buy it.

Silas returns, sees the record player and suspects Sarah has been unfaithful. He drives her from the house in a rage, whipping her as she goes. Silas hates white people and has worked ten years to own his farm free and clear. He is livid that Sarah has slept with a white man, and when the white salesman returns in the morning, he first whips and then shoots him. As Silas protests that he does not want to die, but must because he can never be free in a white man's world, Sarah takes Ruth and runs into the hills, where she watches Silas have a gunfight with the white mob that comes to get him. He dies when they burn the house down around him, but he does not make a sound as it collapses on him.

"Fire and Cloud" follows a preacher, Taylor, as he tries to save his people from a wave of starvation. Denied food aid by the white authorities, Taylor must return empty-handed to his church. There he finds a tricky problem. He has been talking about marching in a demonstration with communists, and they have come to visit him in one room. In another room, the mayor and the police chief have arrived to talk to him. Taylor has a history with the mayor, who has done him favors in exchange for his securing peace and order among the black community. However, if the mayor finds out about the communists, Taylor will be in trouble. First Taylor talks to the communists, who try to convince him to further commit to marching. Taylor gives them only vague answers. He then talks to the mayor and the sheriff, who try to convince him not to march. Again, Taylor is vague on what he will do. He successfully gets both groups out of the church without their paths crossing. Then he talks to his deacons. One among them, Deacon Smith, has been plotting to depose Taylor and take over the church.

A car pulls up, and Taylor leaves the deacons to see who is in the car. Whites beat him and throw him in the back, taking him out to the woods. There, they whip him and make him recite the Lord's Prayer, in a move designed to keep him from marching. Taylor must walk back through a white neighborhood, where a policeman stops him but does not arrest him. Once home, Taylor realizes that this beating directly connects him to the suffering of his people, and he tells his son that the march must go on. Seeing that many in his congregation have also been beaten over the night, Taylor leads them in the march through town. He realizes that together, the pain of his being whipped and the strength of the assembled marchers, black and white people in one crowd, are a sign from God. The whipping is fire, and the crowd is the cloud of the fire and the cloud God used to lead the Hebrews to the Promised Land.

"Bright and Morning Star" concerns an old woman, Sue, whose sons are communist party organizers. One son, Sug, has already been imprisoned for this and does not appear in the story. Sue waits for the other son, Johnny-Boy, to arrive home when the story begins. Though she is no longer a Christian, believing instead in a communist vision of the human struggle, Sue finds herself singing an old hymn as she waits. A white fellow communist, Reva, the daughter of a major organizer, Lem, stops by to tell Sue that the sheriff has discovered plans for a meeting at Lem's and that the comrades must be told or they will be caught. Someone in the group has become an informer. Reva departs, and Johnny-Boy comes home. Sue feeds him dinner, and they discuss her mistrust of white fellow-communists. Then, she sends him out to tell the comrades not to go to Lem's for the meeting.

The sheriff shows up at Sue's looking for Johnny-Boy. The sheriff threatens Johnny-Boy, saying that if she does not get him to talk, she had best bring a sheet to get his body. Sue speaks defiantly to the sheriff, who slaps her around but starts to leave. Then Sue shouts after him from the door, and he returns, this time beating her badly. In her weakened state, she reveals the comrades' names to Booker, a white communist who is actually the sheriff's informer. Sue realizes that she is the only one left who can save the comrades, and she dedicates herself completely to this task. Remembering the sheriff's words, she takes a white sheet and wraps a gun in it. She goes through the woods until she finds the sheriff, who has caught Johnny-Boy. The sheriff tortures Johnny-Boy before her eyes, but she does not relent or try to get Johnny-Boy to give up. Then Booker shows up, and she shoots him through the sheet. The sheriff's men shoot first Johnny-Boy and then Sue dead. As she lies on the ground, she realizes she has fulfilled her purpose in life.