Desperation by Stephen King, is a horror novel set in modern day, about a group of tourists who are captured by an evil spirit as they attempt to pass through a section of US Highway 50, in remote Nevada. The novel tells of the desperate struggle between the evil spirit and the two characters who represent good. David Carver, a young boy whose family has rented an RV for the trip, has recently had a profound religious experience, and feels God is speaking to him directly. Johnny is an aging writer, who is in search of something that will make him feel human again.

The evil spirit is Tak, who has mistakenly been released from imprisonment in a nearby copper mine. He cannot move about unless he is occupying a human body, or a body strong enough to hold him, such as a wolf or an eagle. As he possesses a body, he causes death and destruction, even to the body he is in. At the beginning of the novel, Tak has possessed the strong body of Collie, the town police man.

The group of humans who band together to escape, then fight this evil spirit are: Ralph and Ellen Carver, their daughter Kirsten, and son David; Peter and Mary Jackson, Stephen Ames and a hitchhiker named Cynthia; Tom Billingsley, local vet; Audrey the mining engineer; and Johnny Marinville, writer and motorcycle rider.

The beginning chapters introduce the major characters, and reveal the high level of danger for the humans. Kirsten is killed by Tak, who quickly kills Peter Jackson. Mary struggles to kill Tak, but her unfamiliarity with a gun prevents her from causing him any damage. The remaining group is locked in the police station cells. Tak takes Ellen Carver with him to the mine. David, responding to a voice in his head, lathers himself up with soap and squeaks through the cells. He finds a key to the cells and releases the rest of the people. Tom suggests they hide in the abandoned movie theater until the dust storm subsides. In the meantime,

Stephen Ames is on his way to find Johnny after a confusing cell phone call he received just as Johnny was being arrested by Collie. Stephen picks up a young hitchhiker, Cynthia, and the two head toward Desperation. They try to find help at the mine and encounter strange statue fragments that make them feel violently sexual. They are able to resist the urges and decide to go into town. They see many strange events and Cynthia's intuition keeps them away from the police station. A very strong dust storm is coming, and visibility is reduced, but Johnny sees the van go by and uses his cell phone to contact Stephen and tell him to come to the theater. Just before they reach the theater, Stephen and Cynthia find Audrey and bring her with them.

The group assesses their situation as the storm batters the movie theater. They have encountered many gruesome dead bodies, hordes of rattlesnakes, scorpions and spiders, and yellow-eyed coyotes that follow the humans around. The group has no communication with the outside world and are realizing they are the only live people in the town. They are beginning to realize that Collie is no longer human, but they have no understanding of what he really is. They are also realizing that David Carver, although just a boy, has power beyond those of a human, and he attributes his abilities to God speaking inside him.

Tom Billingsley is attacked by a cougar who comes through the window, but is able to tell Stephen something is wrong with Audrey before he dies. Audrey becomes evil, partially possessed by Tak, and tries to kill David. Tak, now in Ellen's body, comes to the theater and steals Mary. David lapses into a trance-like state and has a very vivid dream. He travels back to the place where he had his religious experience, a platform built by himself and his best friend Brian. David had gone to that platform the day he got out of school early to visit his friend Brian at the hospital. Brian had been in a terrible accident and was dying. David prayed for Brian, and God spoke to him. God told David to leave his school excuse pass at the platform, a place he and Brian had named "Viet Cong Lookout," so he left it at the sign. In this dream, a man in his twenties is David's guide, and talks to him about the mine where Tak was from, about God, and about Brian. When David wakes up, he tells everyone they must band together to fight Tak, at the China Pit.

Johnny is against the idea, and leaves the others. He goes to the mine office and tries to find keys to the ATV. David finds Johnny's wallet, sees a picture of Johnny as a younger man, and realizes this is the man who guided him in the dream. He tells everyone else to go to the China Pit to help Mary, and he rushes off to find Johnny. When he and Johnny meet up, the conversation turns to God and what He wants the group to do, and Johnny finally stops resisting and joins up with David.

Johnny and David take one of the ATV's to the pit and find the others. Mary has escaped from Tak and is with them. The ones who are left are David, Johnny, David's father Ralph, Stephen, Cynthia, and Mary. They all look to David for guidance and he tells them they must find the explosives and cause the mine to fall back in on Tak, imprisoning him again. As the group makes its way to the bottom of the mine, Johnny takes Stephen aside and asks him to hold onto David when Johnny tells him to do so, saying that David thinks he is to sacrifice himself but it will be much more difficult than that.

As the group compiles the explosives, they know they will encounter Tak again. Tak used up Ellen's body before he could transfer to another human, so he took the body of an eagle and hid in the mine. As the group reaches the bottom, Tak attacks David, but Ralph comes between them and saves David. Ralph dies and David is determined to die as well, defeating this creature who has taken his whole family. Johnny signals Stephen, who drags David out of the mine to safety. Johnny stays behind when all the others are gone, and explodes the mine. Mary comforts David, and as they are all leaving Desperation, David finds the school early excuse pass, the one he left nailed to a tree in Ohio, in his pocket, and there is a message from Johnny saying that God is Love.