Off the Salinas River in California, two migrant workers, George and Lennie, travel to a ranch for work.
George and Lennie begin working on a new ranch. The boss's son, Curley, instantly dislikes the mentally disabled Lennie.
Curley’s wife creates problems by constantly seeking the men's attention. The boys make friends with the ranch hands, especially Candy, an old “swamper"
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.
After Lennie killed Curly's wife, he 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.
Lennie was given specific instructions by George that if anything bad happened he should hide near the river. George meets him there. George shoots Lennie before Curley can find him. The men cover it up.