Two itinerant farm workers, George Milton and his simple-minded friend, Lennie Small, are forced to flee armed men after Lennie rips a woman's dress while trying to feel its material. They jump on a train and arrive at Soledad, California, where they take jobs as ranch hands. As they walk, George sees Lennie is carrying a dead mouse. George throws the mouse away, causing Lennie to cry that he misses the woman who gave him mice to play with. George reminds Lennie that the woman was his Aunt Clara, who stopped getting him pets because Lennie kept killing them by petting too hard. George promises Lennie a puppy if he stops crying. At nightfall, George tells Lennie to gather firewood so he can cook some beans, and becomes irate when Lennie whines about not having ketchup. George yells that Lennie has ruined his life by always getting into trouble. A contrite and confused Lennie offers to run away and live in a cave, but George mutters that Aunt Clara would not like him wandering off on his own. That night, George recites an oft-told dream of him and Lennie buying their own ranch, with lots of rabbits for Lennie to feed. Commanding Lennie to look around and remember where they are, George instructs him to return to this spot and hide in the bushes if he gets in trouble. In the morning, they arrive at the Tyler Ranch, where they meet an old, one-handed man named Candy. He takes George and Lennie to meet the "Boss," who yells at them for being a day late. During the interview, George explains that Lennie is his cousin and was kicked in the head by a horse when he was child. After stepping out of the ranch house, George admits to Lennie he lied about the horse and being cousins. Candy shows them the bunkhouse, where they run into the boss's son, Curley, a short man wearing one black glove. Curley demands to know why Lennie is late, and orders George to shut up and let Lennie talk for himself. After Curley leaves, Candy explains that Curley is a boxer, but still has a little man's dislike for anyone bigger than he is. George warns Lennie to keep clear of the boss's son. Curley's young and attractive wife pretends to look for her husband, but it is only an excuse for her to check out the new ranch hands. Her flirting turns George away, and he warns Lennie to stay away from her. At noon, the laborers arrive, including Slim, their foreman, and another ranch worker named Carlson, who asks Slim about his dog's puppies. When Slim says he drowned three because the mother could not produce enough milk, Carlson suggests they kill Candy's old mongrel and give him one of the surviving pups. After a hard day of haying, George asks Slim if Lennie can have one of the puppies. Impressed by how hard Lennie worked, Slim agrees. However, George informs Lennie that the puppies are too young to be separated from their mother, so Lennie beds down with the dogs. The next day, a mule throws a shoe and Slim orders George to take it to the barn. He arrives to find Curley's wife waiting, but her attempt to seduce him is interrupted by the arrival of "Crooks," a hunchbacked African-American stable man, and Curley. When Curley demands to know what George is up to, he answers that he is minding his own business. Curley warns he will beat George if he ever finds him minding his own business with his wife again. That night, Carlson and Slim pressure Candy into letting Carlson put his old dog out of its misery. When Candy hears the shot, he curls up on his bunk and cries. The next day, George tells Slim he lived near Lennie's Aunt Clara, and picked on Lennie when he was a boy. One day, they were playing near a river and George ordered Lennie to jump in. Lennie did, but could not swim, and almost drowned. When George got him to dry ground, Lennie forgot it was George who told him to jump in. From that moment on, George felt responsible for his friend, and when the aunt died, the two hit the road together. That night, George tells Lennie he knows of a farm they could buy when they get a few more dollars. Candy overhears and offers $350 dollars out of the $600 they need if they take him with them, because he is getting too old to work. George agrees. When Curley accuses Slim of sleeping with his wife, the foreman threatens to beat the little man. Seeing Lennie smiling about the farm, Curley thinks he is making fun of him. He punches Lennie in the face. The large man refuses to defend himself, until George yells for him to "get him." Lennie grabs Curley's hand and crushes it. Slim orders Curley to tell the boss he got his hand crushed in a harvester, and threatens to expose what really happened if he refuses. As George cleans the blood off his friend's face, Lennie asks if he can still feed the rabbits. The next night, George goes to town with the other men and leaves Lennie with the puppies. Later, George returns and finds Lennie talking to Crooks in the barn. As he walks Lennie to the bunkhouse, they meet Curley's wife, who wants to talk to someone, but George refuses, and she runs away in tears. The next morning, Curley's wife finds Lennie crying over the corpse of a puppy he accidentally killed while petting it too hard. Instead of leaving, she talks to Lennie about her dreams of being a movie star, and how she married Curley to be free of her mother. When Lennie states he likes stroking soft things, she suggests he touch her hair, but Lennie cannot control his strong hands. As he musses her hair, Curley's wife screams, and with his attempt to silence her, he accidentally breaks her neck. Lennie runs to the stream and hides in the bushes where he earlier agreed to go in times of trouble. Candy later finds the dead woman, and informs George. He believes Curley will lynch Lennie, but George vows he will not let anyone hurt his friend. The other men form a posse, and Slim tells George he can let Curley shoot Lennie or watch his friend go to jail. George steals a pistol and goes to the stream, where he finds Lennie. Hearing dogs approaching, George stands behind Lennie and regales him with dreams of a ranch full of rabbits, then shoots him in the back of the head.