The story begins with Jessie Burlingame and her husband Gerald in the bedroom of their secluded cabin in western Maine, where they have gone for an off-beat romantic weekend. Gerald, a successful lawyer with an aggressive personality, has been able to reinvigorate the couple's sex life by handcuffing Jessie to the bed. Jessie has been into the game before, but suddenly balks. As Gerald starts to crawl on top of her, pretending her protests are fake, she kicks him in the stomach and in the groin, and he then falls from the bed to the floor, hits his head, has a heart attack, and dies.
Jessie is alone in the cabin and unable to move or summon help. There is nothing to do but see if anyone shows up. As days pass and Jessie becomes more desperate, she must face a traumatic incident in her childhood to overcome the circumstances and leave the bedroom alive.
During her ordeal she is visited by a mysterious stranger that she calls the Space Cowboy, although she is not sure if he is real or if she is just halucinating.
The audiobook version of Gerald's Game is read by Lindsay Crouse, who also read the audiobook version of Misery.