George and Lennie are migrant workers. They are expected to immediately begin work at a California farm, and they have just been let off a bus miles away from it. Lennie is described as being an extremely large man with a “shapeless face,” while George is said to be small and dark, with “sharp, strong features.” They seem to be opposites in physical appearance. The two men find themselves extremely thirsty, and they go to a pool in a clearing. They decide that they will camp there for the night. The two talk, and it becomes evident that Lennie has a mental disability, although mild. He clearly feels dependent on George for guidance and protection, and he is devoted to him. It is discovered that Lennie has been carrying and petting a dead mouse. This isn’t out of character, as he often inadvertently kills small, soft animals while petting them. George is angry and throws the mouse away, worried that Lennie would contract a disease. George gives the impression that he laments having to take care of Lennie, as life would be easier without him. However, it is easy to perceive that the two men are mutually devoted friends. He and Lennie dream of purchasing land and farming it. George is pleased by George assuring him that they could keep rabbits. The evening ends with George telling Lennie a story about what their lives would be like if they achieved their dream, conveying an idyllic setting.
The men go to the ranch where they are to work the next day. They worry about what the boss will think about Lennie, and George says that he will do the talking. He tells a lie, saying that they travel together only because they are cousins. He claims that Lennie was kicked in the head by a horse when he was a boy. The men are hired. They meet an old handyman, or “swamper,” called Candy. He is missing one hand and has an extremely old dog. They also meet the boss’s son, Curley, who is mean-spirited and difficult. Curley has recently married, and he is very possessive of his wife. His wife tends to be flirtatious, and Curley is always suspicious and jealous. When George and Lennie are left alone in the bunkhouse, Curley’s wife makes an appearance. She flirts with them, and Lennie says that she is “purty.” George, however, knows how much trouble they could get into from any kind of involvement with this woman. He tells Lennie to ensure he steers clear of her. Soon after this, the ranch-hands comes back from the fields to eat lunch. George and Lennie become acquainted with Slim, a skilled mule driver. Slim has a lot of authority on the ranch. Slim makes a comment on how rare it is to see friendships as close as that between George and Lennie. Another ranch-hand called Carlson says that as Slim’s dog has just had puppies, Candy should have a puppy and shoot his old dog.
The following day, George tells Slim that he and Lennie are not really cousins but rather have been friends since they were little boys. He lets him know how Lennie has done many things that have gotten them into trouble. For example, they had to flee their most recent job because Lennie had attempted to touch a woman’s dress and ended up being accused of rape. Slim says that he will give Lennie a puppy, and Carlson keeps on pressuring Candy to shoot his old dog. Candy gives into this suggestion when Slim agrees that death would be a mercy for the suffering dog. Before Carlson brings the dog outside, he promises that he will make sure that the death is painless.
Curley is frantically looking for his wife, and he goes to the barn to confront Slim. Candy hears Lennie and George talking about their dream of having land of their own, and her offers them everything he has saved if they will let him live with them. The three men agree never to tell anyone else of their plan. Slim goes back to the bunkhouse, angry with Curley for his suspicions. Curley wants a target for his fury, and he picks a fight with Lennie. As they fight, Lennie injured Curley’s hand. Slim tells Curley that if he makes George and Lennie lose their jobs, everyone at the farm will laugh at him.
Most of the men go to a local brothel the next evening. Lennie stays behind. He finds himself with Crooks, a black stable-hand who always seems to be lonely, as well as Candy. Curley’s wife appears and flirts with them. She won’t leave until the other men come back. She sees that there are cuts on Lennie’s face. As a result, she realizes that her husband, Curley, was injured by him instead of a piece of machinery (as he had said). She finds this idea rather amusing. The following day, Lennie inadvertently kills his new puppy in the barn. Curley’s wife comes in and comforts him. She confides in him that she is disappointed in her life with Curley, and she regrets not pursuing her dream of being a movie star. Lennie says that he loves touching soft things, and she gives him permission to feel her hair. He grabs it too forcefully, and she yells. He accidentally breaks her neck in trying to silence her.
In a panic, Lennie rushes to the pool of the Salinas River that he and George had decided on as a place to meet if either of them ever got into trouble. When the men at the ranch see what has occurred and gather as a lynch party, George comes to Lennie. Lennie is surprised when George isn’t angry at him for the “bad thing” he has done. George starts telling Lennie the story about the farm they dream of owning one day. As he talks about the rabbits they will have, they can hear the lynch party approaching. George reaches over and shoots Lenny in the back of the head.
The lynch party arrive, and George lets them think that Lennie was the one with the gun. He indicates that he tried to take it away from him and accidentally shot him. Slim is the only person who realizes what has really occurred: that George killed Lennie out of mercy. Slim consoles him and leads him away. The other men are confused.