Famed novelist Paul Sheldon is the author of a successful series of Victorian romance novels featuring a character named Misery Chastain. Wanting to focus on more serious stories, he writes a manuscript for a new novel that he hopes will launch his post-Misery career. While traveling from Silver Creek, Colorado to his home in New York City, Paul is caught in a blizzard and his car goes off the road, rendering him unconscious. A nurse named Annie Wilkes finds Paul and brings him to her remote home.
Paul regains consciousness and finds himself bedridden with broken legs and a dislocated shoulder. Annie claims to be his “number one fan” and talks a lot about him and his novels. Out of gratitude, Paul lets Annie read his new manuscript. While feeding him, she is angered by the profanity in his new work and spills soup on him, but apologizes. Soon after, Annie reads the latest Misery novel, discovers that Misery dies at the end of the book, and flies into a rage. She reveals to Paul that nobody knows where he is and locks him in his room.
The next morning, Annie forces Paul to burn his new manuscript. When he is well enough to get out of bed, she insists he write a new novel titled Misery’s Return, in which he brings the character back to life. Paul complies, believing Annie might kill him. One day, when Annie is away, Paul begins stockpiling his painkillers. He tries poisoning Annie during dinner but fails after she accidentally knocks over her glass of wine that he had spiked with his crushed painkillers. Paul later finds a scrapbook of newspaper clippings about Annie’s past. He discovers that she was tried for the deaths of several infants, but the trial collapsed due to lack of evidence. Annie had quoted lines from his Misery novels during her trial. Annie later drugs Paul and straps him to the bed. When he wakes, she tells him that she knows he has been out of his room and breaks his ankles with a sledgehammer (she calls it Hobbling) to prevent him from escaping again.
The local sheriff, Buster, is investigating Paul’s disappearance. When a shopkeeper informs the sheriff he has sold Annie considerable quantities of typing paper, Buster pays Annie a visit. When he finds Paul drugged in the basement, Annie fatally shoots Buster with a shotgun; she tells Paul that they must die together. He agrees, on the condition that he must finish the novel in order to “give Misery back to the world.” He conceals a can of lighter fluid in his pocket.
When the manuscript is done, Paul asks for a single cigarette and two glasses of champagne, as is his usual ritual when completing a book, to which Annie complies, when she leaves, he sets the manuscript on fire in front of her. As Annie rushes to save it, Paul strikes her with the typewriter and they engage in a violent struggle, with Paul stuffing her mouth full of the burned novel in retaliation, and suffering a gunshot wound to the shoulder from Annie’s revolver. Annie gets up and steps forward to attack Paul, who trips her and she hits her head on the typewriter. Believing she’s dead, Paul crawls out of the room, but Annie suddenly springs back to life and attacks him once again. Paul grabs a metal doorstop and viciously bashes her in the face, finally killing her.
Eighteen months later, Paul, now walking with a cane, meets his agent, Marcia, in a restaurant in New York City. The two discuss his first post-Misery novel, and Marcia tells him about the positive early buzz. Paul replies that he does not mind and that he wrote the novel for himself as a way to help deal with the horrors of his captivity. Marcia asks if he would consider a non-fiction book about his captivity, but Paul declines as he is obviously suffering some kind of psychological trauma from his experiences, and often suffers nightmares and hallucinations of Annie coming to get him for revenge. Just as he says that, Paul sees a hallucination of Annie approaching but in actuality it is a waitress, who tells Paul that she is his number one fan. Paul meekly replies “That’s very sweet of you.”