Off the Salinas River, in California, two migrant workers, George and Lennie, travel to a ranch for work after leaving a previous job because Lennie mistakenly grabbed a woman by her dress.
Lennie and George are friends. However, Lennie is developmentally disabled, and because of his childlike mentality, the two friends often find themselves in trouble.
Curley, the boss’s son, immediately takes a dislike to Lennie and picks on him. Curley’s wife creates problems by constantly seeking the men's attention. The boys make friends with the ranch hands, especially Candy.
Lennie was given a puppy by Slim and is in the barn tending it. Curley’s wife enters and they begin to talk. Without realizing it, Lennie grabs her hair, because he likes soft things. When she gets nervous and tells him to stop, he panics and breaks her neck.
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. The reader feels the sorrow of George having to kill his best friend.