The novel begins with Demon, the protagonist of the story, recounting the troubled circumstances of his birth. He was born to a single mother in a trailer park in Lee County, Virginia, part of southern Appalachia. He says that he quite literally slid out of her without her noticing. Demon's father dies before he is born. He is told that it was the result of a terrible car crash, but later learns otherwise. He gets the nickname Demon from a young age and is sometimes referred to as "copperhead," because of his red hair, inherited, he is told, from his father.
He grows up with his mother as a somewhat absent figure, as she struggles with drug addiction and starts dating a cruel man named Stoner. He also spends a great deal of time with his neighbors, the Peggot family, including the elderly Mr. and Mrs. Peggot, children Maggot and Emmy, and June, Maggot's aunt. His mother eventually marries Stoner. Things at home are tense for Demon, as Stoner often bullies him while his mother stands idly by. This situation reaches a breaking point when his mother overdoses and is sent to a rehab facility. Demon is taken as a ward of the state and sent to live in foster care. He asks to live with the Peggots, but is denied.
He ends up at a farm owned by an elderly man named Crickson. Crickson uses the foster care system to get free child labor for his tobacco farm. Demon befriends another boy named Tommy. All the boys in the house follow the lead of an older boy nicknamed Fast Forward. Fast Forward is a quarterback for the Generals, the local high school football team. He convinces the other boys to give him money, take his punishments, and take pills. Things get increasingly bad when Demon's mom dies from a subsequent overdose.
Demon is heartbroken and full of rage. The funeral is held. He then spends time with the Peggots. He hopes they will formally adopt him, like they did for Emmy and Maggot, but they do not. He is sent to live with the McCobbs, an impoverished family who constantly hopes to make money through get-rich-quick schemes. They force him to get a job, picking through garbage. He learns later that his boss was running a meth lab. He saves up money and eventually decides to run away from home.
He takes his money and hitches across Tennessee to Murder Valley, his father's hometown, in hopes of locating his grandmother. He has all of his money stolen at a gas station and overshoots his destination. After several trips, he finally makes it to Murder Valley and finds his grandmother. She is a much older woman who lives with her brother, Mr. Dick, a disabled man in a wheelchair with a small, child-like body. Demon befriends Mr. Dick, who talks to him about his love of reading. Eventually they find him a suitable home with a football coach.
Demon says that the early years with Coach, as he refers to him, are some of the happiest of his life. He befriends Coach's daughter, Agnes, nicknamed Angus, and the two become close friends. The family is wealthy, so he is able to get nice new clothes and school supplies. Because of his proximity to Coach, Demon becomes popular at school. After some time passes, the coach begins to prepare him to play football, remarking that his strong build will likely make him a great tight end. He becomes even more popular at school and starts to attract the attention of girls.
Things continue to be good until Demon suffers a bad injury on the football field. Prescribed painkillers, Demon soon begins to fall into the grips of addiction. He tries to get back on the field but is unable to play as well as he used to. Around the same time, he falls in love with a girl named Dori. She is also addicted to opiates and as they become more and more involved he continues to become more dependent on painkillers. Eventually they move in together, much to everyone’s concern. He flunks out of school and has to stop playing football. Things look increasingly dire, as everyone around him is also an addict, including Emmy and Maggot. Mr. Peggot dies and Emmy begins dating Fast Forward. She disappears with him for several months. June is worried and furious.
Demon learns that Emmy has been abandoned by Fast Forward. He, Maggot, and June travel to Atlanta, working off a tip from one of Emmy's friends. They pick her up from a dilapidated house and take her home. June sends her to rehab. Shortly after this, Dori overdoses and dies. Demon feels numbed by the loss. Later, while hanging out with Maggot, Demon is told that Fast Forward is hanging out at a local swimming hole. High on drugs and extremely angry, Demon and Maggot head over to find him, crossing paths with Emmy's kind ex-boyfriend, Hammer. The three of them find Fast Forward. Fast Forward falls and cracks his skull open, dying on impact. Hammer dives in after him and drowns. Demon is devastated by the loss. He feels that he should have died instead of Hammer, as Hammer was a better person than he.
Eventually, Demon goes to a halfway house and gets sober. He also gets more serious about art, publishing a comic strip online. Three years pass, and he receives an offer to write a graphic novel. He returns to Lee County to discuss the contract with Ms. Annie. He also visits Coach and June. Finally, he spends time with Angus, realizes she is in love with him, and they drive to the ocean together. He feels free and elated.
