George and Lennie stop by the Salinas River to sleep on their way to starting their new jobs at the ranch in Soledad. George tells Lennie off for keeping a dead mouse (which he has accidentally killed by petting it) and Lennie threatens to leave George, but George talks him out of it.
Lennie asks George to tell him about their dream. George describes owning their own home and land, where they would grow vegetables and rear animals and become self-sufficient.
The following morning, George and Lennie go to the ranch where they meet Candy (an elderly handyman) and the Boss in the bunkhouse. The Boss questions them and is suspicious when George answers for Lennie, but he allows them to stay.
George and Lennie meet other people on the ranch, including Curley (the Boss’s son) who takes a dislike to Lennie, and Curley’s wife, who flirts with the men.
After work, the ranch hands return to the bunkhouse and complain about the smell of Candy’s old dog. Carlson (a ranch hand) convinces Candy to allow him to shoot the dog, saying it is kinder because he is suffering.
Candy, upset about the death of his dog, discusses the dream with George and Lennie. He says that he has some money put by and asks to join them in purchasing some land. The dream seems more possible.
Curley enters the bunkhouse and picks a fight with Lennie, who cannot cope. George tells him to fight back and he crushes Curley’s hand.
On Saturday evening, most of the men go to town to a brothel, leaving behind Lennie, Candy and Crooks (the only black man on the ranch). Curley’s wife also remains at the ranch. Lennie goes to speak to Crooks, joined later by Candy. They discuss the dream and Crooks also asks to get involved. Curley’s wife interrupts them and threatens Crooks when he asks her to leave. Upset and angry, Crooks tells Lennie and Candy to leave and says he no longer wishes to be part of the dream.
On Sunday, Lennie accidentally kills a puppy that he has been given by Slim, the leader of a grain team. While he is trying to hide the puppy in the barn, Curley’s wife joins him. She talks to him and invites him to stroke her hair. While doing this, he unintentionally kills her by breaking her neck then runs away.
Curley’s wife’s body is found by Candy. He alerts the other men who go out to look for Lennie with guns, planning to shoot him. George finds him first (in the place they camped at the start of the book) and shoots him in the back of the head.