It is the time of the Great Depression in America, and two men have traveled across the country in search of work: George Milton, a street smart young man; and Lennie Small, a mountain of a man with strength to match, but with significant mental and emotional disabilities. In their travels, they happen upon a ranch that is in need of laborers. Lennie, who has a fondness for anything soft and a tendency to get into trouble, is cautioned by George not to cause any trouble while they are at the ranch, lest they have an incident like in the last town where Lennie touched a woman's dress. In exchange for his good behavior, George reminds Lennie that once they finally make the money they need to start a farm of their own, Lennie can play with all of the rabbits he wants.
The following morning, George gets himself and Lennie hired on by the ranch's own as laborers. They are introduced to the other ranch hands, including the owner's son Curley: an amateur boxer with a hair-trigger temper and a complex about larger men, including Lennie. At first, George and Lennie's fortunes appear to finally be taking a turn for the better as they make fast friends with most of the other ranch hands, one of whom — Slim — offers Lennie a puppy to fulfill his desire for soft things, while another — Candy — offers to help fund George's plan for his own farm in exchange for being able to live with them. Trouble still brews when Curley picks a fight with Lennie. Lennie refuses to fight back at first, but with George's encouragement, Lennie is able to easily break Curley's hand.
Also posing a problem is Curley's wife, who is dissatisfied with her current lot in life and bonds quickly with Lennie. One fateful day, after Lennie accidentally strangles the puppy he had been gifted, Curley's wife approaches him and confides in her dreams of starring in movies. Learning of Lennie's affinity for soft things, she offers to let him touch her hair. Unfortunately, Lennie finds difficulty in restraining his strength, scaring Curley's wife. When she screams in fright, Lennie reflexively holds tighter to her neck until, tragically, he breaks it, killing her.
Lennie flees in fear, and the other ranch hands find the body of Curley's wife shortly afterwards. A lynch mob is swiftly formed to hunt down Lennie, and George realizes all too well that this is the end of their dream of their own farm. As the lynch mob searches for Lennie, George manages to find him first by the river, where they agreed to meet should they find themselves in trouble again. Even though it was no longer attainable, George and Lennie speak once more about their dream farm. As Lennie, who knows about their dream by heart, excitedly talks about being able to play with the rabbits, George, hearing the lynch mob fast approaching, shoots Lennie once, killing him instantly — a more merciful end to his life than allowing the lynch mob to get their hands on him. Once the mob arrives, Slim, who had to put down his beloved dog days earlier, realizes what had happened and accompanies George as he mourns the loss of his friend...
