Two displaced ranch workers, George and Lennie, travel through California during the Great Depression, searching for job opportunities. George is small, wiry, and quick-witted, while Lennie is large, physically strong, but mentally impaired. Despite their stark differences, the two men share a deep bond; George looks after Lennie to keep him out of trouble while Lennie dreams of tending rabbits on a piece of their own land. They secure jobs on a ranch and form tentative alliances with other workers. However, Lennie's inability to control his strength and understand the consequences of his actions leads to tensions with the ranch owner's aggressive son, Curley, who is suspicious and jealous of Lennie's remarkable strength.

As time passes, Lennie's innocent fascination with soft things inadvertently causes trouble. His interactions with Curley's flirtatious wife further escalate the situation. The fragile balance George and Lennie try to maintain starts to unravel due to the impending conflicts and rising suspicions among the ranch hands. Their shared dream of owning a piece of land becomes an ever-distant hope as the consequences of Lennie's behavior grow more severe, putting their friendship and future in jeopardy.