Sing, Unburied, Sing opens in rural Mississippi, where we meet 13-year-old Jojo, a biracial child who is forced to grow up far faster than he should due to the tumult and trauma he endures. Jojo and his family live with their grandparents Mam and Pop; Mam is not long for this world, as she’s dying of cancer. Jojo's mother, Leonie, struggles with drug addiction and is often absent, leaving Jojo to care for his younger sister, Kayla. During an exceptionally lackluster party for Jojo’s 13th birthday, Leonie learns that her boyfriend Michael—Jojo’s white father—is being released from Parchman Farm penitentiary after being jailed for three years. Pop had also been imprisoned there in his youth, and he often tells Jojo stories about the conditions there and about another inmate, a 12-year-old boy called Richie.
The narrative unfolds through multiple perspectives, initially switching between Jojo's and Leonie's, as they—along with Kayla and Leonie’s friend Misty—set off on a road trip to Parchman Farm to pick up Michael. Along the route to Parchman, the group make a stop to pick up a bag of methamphetamine from two of Misty's acquaintances, a woman named Carlotta and her meth-cooking husband Fred. Jojo is growing desperate to find a remedy for the high fever and vomiting Kayla develops. They spend the night at the home of Al, Michael’s attorney, and a fellow drug addict, during which time Leonie tries unsuccessfully to concoct an herbal remedy for Kayla. She can’t remember the cures Mam taught her, and instead makes a concoction of blackberry leaves and sugar which she forces Kayla to drink. She doesn’t stay with Kayla long, however, and soon leaves to get high with Misty and Al. Jojo, worried for her, forces her to vomit up the blackberry leaf mixture.
The next day at Parchman, Leonie and Michael have an intense, passionate reunion as he’s released. While this is happening, Jojo experiences a fleeting vision of cotton-picking men as he looks at the fields around the prison; Kayla seems to see something too. When the group get back to their car, the ghost of Richie, who has been confined to Parchman since his death, makes his first appearance. Richie wants to go with them, as he believes that learning the truth about his death from Pop will allow him to pass on to the next life. From this point onwards, some of the chapters are told from his perspective.
On their way back to Bois Sauvage, a hostile police officer forces them to pull over. Leonie, fearful of being caught with drugs, swallows their entire stash of meth as they are pulled over. As soon as she admits they have come from Parchman, she and Michael are forced out of the car and handcuffed. There’s a nerve-wracking moment where the young, nervous officer points his gun at Jojo, but when Kayla vomits explosively on him the group is eventually allowed to leave the scene. They continue their journey, but it’s clear that the leaky bag of meth is leaching into Leonie’s system, causing the beginnings of an overdose. Michael then tells Jojo to buy milk and charcoal, and uses the nauseating mixture to make Leonie vomit, saving her life. She throws up the plastic bag of drugs as the ghost of Given, Leonie's deceased brother, watches. Finding Mam and Pop gone upon their return to Bois Sauvage, Michael insists on stopping at his parents’ house so Kayla and Jojo can meet their grandparents. Although Leonie is hesitant and still extremely high, she consents. The meeting is a disaster: Michael’s father Big Joseph is a racist who disapproves of Michael and Leonie’s relationship, and he quickly begins to curse at Leonie and the children, using the n-slur and criticizing Michael for their relationship. Michael, infuriated, headbutts him, and after a brief tussle he bursts out of the house. Maggie, Michael’s mother, briefly stops him and the two embrace, and then the group drives away. They head back to Mam and Pop’s, where Pop informs Leonie that Mam is close to dying. Leonie visits her mother, who instructs her to fetch objects for a ritual that will help call forth Maman Brigitte, a Vodou mystère she believes can guide her to the afterlife. Leonie is reluctant, but eventually relents. She goes to fetch the ritual objects Mam asks for.
Meanwhile, Richie urges Jojo to convince Pop to complete the story of his life. Jojo eventually agrees, and discovers from Pop that Richie was compelled to escape Parchman with a fellow inmate named Blue. Richie was thinking of running anyway, but when he accidentally saw Blue beating and raping a female inmate, Blue forced him to escape then and there. When Blue attempted to rape a white girl, who then reported him, the white people from the nearby area formed a lynch mob and set out to murder him. When they caught him, they tortured him and dismembered him before burning him to death. Knowing a similar fate awaited Richie, Pop used the Parchman dogs he was assigned to train to find him, and quickly ended his life to spare him from torture. He was able to pass off Richie’s death as an attack by his dogs, but tells Jojo he has always felt guilty for his part in it, smelling Richie’s blood for the rest of his life. The two collapse to the ground together weeping, and Richie’s spirit sucks all the air around it into a black core before imploding. As this happens, Given appears to Leonie to warn her but is himself sucked out of the house and into Richie’s orbit. He disappears, and Kayla begins to cry, saying that a Black boy and a black bird want to take Mam. Leonie tries to reassure her that nothing is wrong, but when she opens the door to Mam’s room it’s very clear that something terrible is happening.
Mam’s room stinks as though she’s lost control of her bowels, and she tells Leonie through gritted teeth that she can hear a vengeful ghost, a boy looking for his mother. There follows a confusing scene where the entire family are in the room, but as Leonie can’t see or hear Richie it’s unclear what is happening. Given speaks at last, repeating that Mam is not Richie’s mother. As Leonie invokes Maman Brigitte, Given, Richie, and Mam appear to struggle. Leonie says the litany that invokes Maman Brigitte, as Mam requests. Jojo tells Richie that he got what he came for, and Given also tells him to go. Jojo sees Given for the first time, and they greet each other before Given tells Mam he’s come to take her and lies down with her in an embrace. Mam dies.
Given’s spirit vanishes with Mam's last breath. Everyone is weeping, but Jojo confronts Leonie, accusing her of causing Mam’s death. Leonie is furious and heartbroken, and she begins to beat him until Pop stops her. In her sorrow, Leonie turns to Michael and to meth, looking for a way to dull her guilt. She begs to leave, even if only briefly, and Michael takes her back up north to Al's. As the story draws to a close, Michael and Leonie's involvement in their children's lives diminishes even further. Jojo, Pop, and Kayla make do as best they can. Eventually, when out on a long walk, Jojo encounters Richie again. He hasn’t successfully moved on, and reveals a terrifying tree to Jojo. It’s full of Black souls who came to violent, unjust ends, like himself. They speak to Jojo with their eyes, revealing their horrible deaths, which are all implied to be racially motivated crimes. Jojo is frightened and appalled, standing frozen for hours. However, Kayla and Pop eventually find him, and Kayla begins to sing a nonsense version of a lullaby Leonie had sung when she and Jojo were babies. The energy of the treeful of ghosts changes, becoming relieved and appreciative as her song reminds them of the time before they were born. Jojo, Pop, and Kayla walk away as the ghosts repeatedly and contentedly chorus the word “home.”