The first chapter is told from the perspective of Jojo on his thirteenth birthday. Jojo’s grandmother, Mam, is undergoing chemotherapy (a treatment for cancer), so she sleeps a lot. Jojo and his grandfather, Pop, slaughter a goat for the family to eat. Jojo’s other grandfather, Big Joseph, is white, and Jojo has only met him a couple of times. Jojo’s father, Michael, has many tattoos, some of which he got in prison. After they kill the goat, Pop sends Jojo back inside, saying he heard Jojo’s three-year-old sister, Kayla, crying. Jojo finds that Kayla isn’t crying. Jojo explains that nowadays he calls his mother by her first name, Leonie, rather than “Mama.” He recalls a time just after Mam was diagnosed with cancer, when his grandparents left him alone with Leonie. Leonie left Jojo alone, and while she was gone Pop’s brother, Stag—who is “sick in the head”—walked past outside. Jojo hid in the barn with the animals and stepped on a jagged can, which caused a fight between Pop and Leonie about whether Jojo was old enough to be left alone.
Back in the present, Pop tells Jojo that he and Stag have the same dad but different mothers. When they were young, Stag would always get into trouble. Once, Stag was beaten by a white man, and later a group of white men tied up Pop and Stag and took them to a work camp called Parchman. One of the boys in the camp, Richie, was only twelve years old. Richie had been caught stealing food to feed his nine siblings. Pop’s story is interrupted when Leonie returns with a birthday cake for Jojo. While the family sings happy birthday, the phone rings and Leonie answers. Jojo knows it is Michael, calling with news that he is getting out of prison this week.
The next chapter is told from Leonie’s perspective. After speaking with Michael, she got extra shifts at the bar where she works, the Cold Drink. Leonie’s coworker at the bar, Misty, gets high on a cocktail of drugs every night. That night, the two of them go to Misty’s, where they do cocaine and talk. Leonie has a vision of her brother, Given, who appears to her whenever she is high. The next day, Leonie and Pop argue over whether she should take Jojo with her to pick Michael up from Parchman. Leonie recalls a time shortly after she got her period, when Mam revealed that certain women in their family, including Mam herself, possess a form of telepathic intuition. In the present, Leonie tells Mam that she is taking the kids to get Michael when he gets out, and Mam suggests that she bring Misty, whose boyfriend is also in Parchman. Leonie suddenly realizes that she is having visions of Given because her mother is about to die. Back in high school, Given was shot by Michael’s cousin on a hunting trip.
The third chapter moves back to Jojo’s perspective. Leonie, Misty, Jojo, and Kayla set off together in the car. As they drive, Jojo stares at Misty’s bra strap and is filled with desire. Later, he finds a tiny leather pouch (the gris-gris bag) folded into his clothes, with a feather inside and a note saying “Keep this close.” He knows it’s from Pop. Jojo recalls Pop telling him about when he was forced to work under a notorious white overseer named Kinnie Wagner at Parchman, who treated Pop like one of his dogs. Leonie stops the car at the house of a white woman (Carlotta) and her little boy. They go inside and see that the house is filled with food and other items purchased in bulk. Jojo wanders out to the shed and peeks inside, where he sees a man (Fred) cooking meth, which Jojo notes is the reason why Michael ended up in prison. Soon after, they all get back in the car and continue on their way.
The fourth chapter returns to Leonie’s point of view. She explains that Michael used to work on an oil rig. One day, there was an accident on the rig, and Michael returned home traumatized. He began using meth. Now, Leonie and Misty are using the road trip to transport meth they picked up at Fred and Carlotta’s house. Kayla throws up in the car, so they stop, and Leonie walks into the bushes nearby, hoping to remember which plants Mam told her could treat nausea. Leonie picks some blackberry plants, which causes her hands to bleed.
The fifth chapter returns to Jojo’s perspective. He doesn’t want Leonie to give Kayla the blackberry leaves, because unlike Mam or Pop, Leonie “ain’t never healed nothing or grown nothing in her life.” Leonie once bought Jojo a fish but wouldn’t buy it any fish food, and thus it quickly died. The car pulls up to another house. Inside, Michael’s lawyer, Al, is making spaghetti. Leonie cooks the blackberry leaves, mixes them with sugar, and feeds the mixture to Kayla. While the adults stay in the other room, Jojo—worried about Kayla, who has a soaring temperature—takes her into the bathroom and forces her to throw up. That night, Jojo tries to sleep, but instead remembers the next part of Pop’s story about Parchman, in which Richie is whipped for accidentally breaking his hoe and Kinnie escapes.
In the morning, Jojo finds Leonie, Misty, and Al on the sofa. They clearly haven’t slept. They leave Al’s house and soon arrive at Parchman. When Michael comes out, he and Leonie passionately embrace. Jojo recalls the last part of the Parchman story. Richie suffered enormously from his injuries, shaking and throwing up even though the wounds didn’t appear to be infected. Eventually, Richie told Pop that he was “going home.” Back in the present, Michael greets Kayla, but she is tense in response. As they drive away, Kayla throws up again. In the midst of the commotion, Jojo sees a young black boy standing by his window. The boy says: “I’m going home.”
Chapter 6 is told from Richie’s perspective. He explains that he immediately knew Jojo is “River’s child.” Richie explains that “in the beginning” he found himself in a pine forest, where he had a conversation with a white snake. He flew into the sky, and remembered the moment he died with River (Pop) beside him. Richie haunted Parchman, but River was no longer there. Richie recalls an enormous white man nicknamed Hogjaw who was also placed in Parchman. He wants to tell Jojo about how River looked after him, but says nothing. No one in the car can see him except Jojo and Kayla.
Chapter 7 returns to Leonie’s perspective. She and the group drive back to Al’s house. Leonie tells Al that Kayla is still sick, and Al fetches some bread and ginger ale for her. In the bathroom, Leonie washes the vomit off Kayla and feels the urge to hit her. She tells Jojo to get Kayla dressed and in bed, then goes to get high and have sex with Michael in the next room. During this time, Leonie sees Given in the room with them. In the morning, they set off again on the road. Al gives them sandwiches to take, and Leonie sees that he is high again.
Leonie explains that she got pregnant shortly after she and Michael got together, when she was 17. Mam disapproved of Leonie’s obsessive, deferential love for Michael. When Leonie told Mam she was pregnant, Mam replied that she’d known for two weeks. Mam asked Leonie if she wanted the baby, offering to make a tea that would terminate the pregnancy, but Leonie said she wanted to keep it. Back in the present, Michael alerts Leonie to a police car nearby. They panic, and do not have time to hide the meth they got from Al, so Leonie swallows it. The police officer informs Leonie that she was swerving, then asks her to get out of the car and show her license and insurance. The officer questions her, and without thinking Leonie tells him that they are coming from Parchman. The officer immediately handcuffs her, then Michael. Jojo gets out of the car too, and when the officer tries to handcuff him, pointing a gun at his head, Kayla runs in front of Jojo to shield him. The officer searches the car, Leonie suddenly gets high from the meth she swallowed, and Kayla throws up. Disgusted, the officer lets them go. Leonie sees Given again.
Chapter 8 is told from Jojo’s perspective. He explains that when the police showed up, Richie warned: “They going to chain you,” then hid on the floor. After the encounter with the police, the group stops at a gas station and Michael gives Jojo money from Leonie’s purse, telling him to buy milk and charcoal, explaining that Leonie is sick and needs it for her stomach. Jojo also buys a Tootsie Pop. Michael force-feeds Leonie the milk and charcoal mixture until she violently throws up. In the car, Richie tells Jojo that he knows he tried to escape from Parchman and failed, but doesn’t know how, and that he needs Jojo to find out. He explains it is the only way for him to get home. Richie says that there is still much Jojo doesn’t know about the world.
Chapter 9 switches to Richie’s perspective. Richie can see that Jojo is more “innocent” than Richie himself had been at thirteen. After Richie died, Parchman pulled him back. Richie explains that River used to see a prostitute in Parchman nicknamed the Sunshine Woman because she always wore yellow. One day, the Sunshine Woman told River and Richie that a black man and his wife had been lynched because a white woman lied that the man had molested her. When Jojo arrived at Parchman to pick up Michael, Richie was awoken by a voice urging him to follow Jojo to River, promising that then he would be able to go home.
Chapter 10 is told from Leonie’s perspective. She reminisces about the first months she and Michael dated as teenagers. She then wakes up in the present, feeling horrific. She sleeps until they arrive back at the house, but Mam and Pop are not there. Michael insists that they go and see his parents, but he and Leonie fight about this. Leonie is holding Kayla when the car hits a wild hog. Kayla bruises her head, briefly loses consciousness, then shouts for Jojo. They arrive at Big Joseph and Maggie’s house, and Joseph tells the family that Leonie, Jojo, and Kayla aren’t welcome inside. Maggie attempts to greet Jojo and Kayla, but Big Joseph gets more and more irate, eventually calling Leonie a “nigger bitch,” which causes Michael to head-butt him. Big Joseph and Michael continue to fight while Leonie and the children wait in the car.
Eventually, Michael gets back in the car and they drive home, where they find Pop sitting outside. Pop urges Leonie to go inside and see Mam, who tells her it’s “time… for me to go.” Mam says she has tried to heal herself, but now must give up. She wants to be possessed by one last mystère, Maman Brigitte, “the mother of the dead.” She asks Leonie to gather the necessary items for the ritual.
Chapter 11 returns to Jojo’s perspective. When they arrive home, Pop tells Jojo to put Kayla to bed. Richie tries to talk to Pop, but Pop can’t hear him. In the morning, Jojo wakes up to the smell of Michael cooking bacon. Michael reminds Jojo about a time when they went fishing together and Michael told Jojo about Given. He promises Jojo that he is now “here to stay.” Kayla fusses and cries, and Michael hits her. Richie begs Jojo to talk to Pop for him, and although at first Jojo is resistant, eventually he agrees. Jojo goes to see Mam, and Mam admits that she has always known Leonie doesn’t have “the mothering instinct” and that she won’t feed Jojo. Jojo asks Mam about death, and she says she probably won’t come back as a ghost because this usually only happens when death is violent.
Chapter 12 is told from Richie’s perspective. In the midst of watching Jojo and his family, Richie has a vision of water, land, a community of houses and people, and the sound of a beautiful song. Richie watches Leonie walk to Given’s grave and ask him to fulfil Mam’s request for the mystère. Leonie then returns to Mam’s room, falls to the floor, and says “Okay.”
Chapter 13 returns to Jojo’s perspective. He explains that the previous night, Richie crawled around the house and sang. Jojo hears Pop destroying a termite-infested old pen outside and goes to help him. Jojo asks Pop about Richie, and Pop explains that Richie succeeded in escaping from Parchman. Pop explains that one Sunday, a man named Blue who “wasn’t right in the head” raped a woman. Richie caught Blue afterward, and the two ended up running right out of Parchman. The prison sergeant and warden, along with a gang of white men, caught them and skinned Blue alive, cutting off parts of his body. Pop was there with the dogs, and, knowing that the white men would come for Richie next, told Richie he would help him get home and stabbed him in the neck. Richie screams, and Pop tells Jojo that he has been haunted by what he did ever since. Richie disappears, and Jojo holds Pop like he holds Kayla.
Chapter 14 is told from Leonie’s perspective. On coming back from collecting the cemetery stones for Mam’s ritual, she sees Given in the house. Kayla is crying, and talking about “the black bird… the Black boy.” They go into Mam’s room, which smells like rot, and Mam says Leonie is “too late.” Given is in this room too, shouting at Mam, who pleads weakly in return. Jojo enters. Leonie arranges the ritual items on the altar, and says the litany for Maman Brigitte. Given, Jojo, and Kayla recognize one another, and then Given embraces Mam, telling her he is taking her home. Mam dies. Everyone cries except Jojo, who is furious at Leonie for summoning the gods that let Mam die. Later, Leonie tells Michael that Mam is dead and asks to go see Al so they can get high. They get in the car and drive off together.
Chapter 15 returns to Jojo’s perspective. He explains that these days he sleeps in Leonie’s bed. She and Michael only come back for a couple of days every two weeks. Michael and Leonie are now both very thin, and sleep on the sofa together. Jojo admits that sometimes, at night, he feels like he understands Leonie and why she has been a bad mother, but that he never has this feeling during the day. Jojo knows that he will not see Mam or Given again, but he still sees Richie, as well as countless other ghosts with different stories of violent death. Kayla, who can see the ghosts too, tells them to go home. Kayla begins to sing, and the ghosts are relieved and say “Yes.” They say: “Home.”