Of Mice and Men opens with the two main characters, George Milton and Lennie Small, walking toward Soledad, California. Steinbeck describes George as: "small and quick, dark of face, with restless eyes and sharp, strong features'' (2). In contrast, Lennie is depicted as George's opposite: "a huge man, shapeless of face, with large, pale eyes, [and] wide sloping shoulders" (2). Steinbeck demonstrates that both men need each other for emotional support. George, though often annoyed with Lennie's childlike and troublesome behavior, recognizes that Lennie keeps him from the aching loneliness of a ranch hand's solitary life. He also recalls his promise to "Aunt Clara" to care for Lennie, who is incapable of caring for himself.
When setting up camp for the night at the Salinas riverbed, George discovers Lennie clutching a dead mouse. In a moment of foreshadowing, Steinbeck shows that Lennie has a habit of stroking soft things and killing them by accident with the force of his grip. George tells Lennie to dispose of the mouse or he is not going to let him tend rabbits on the farm they plan to own one day. George begins to tell Lennie about an idyllic piece of land where they will "[...] have a little house and a couple of acres an' a cow and some pigs and—," as Lennie exuberantly interjects, "an' live off the fatta the lan' [...] An' have rabbits'" (13). The routine reveals that this vision has been a motivating factor in the men's lives for quite some time.
During the first chapter, Steinbeck also reveals that Lennie and George were forced to leave their previous job in Weed, California because Lennie tried to feel the soft fabric of a girl’s dress, and his actions were misinterpreted as inappropriate. As a result of this experience, George decides that when they meet their new boss, Lennie should stay quiet and let George do all of the talking. Their boss becomes suspicious, but he decides to let them stay because he recognizes that Lennie's size and strength will increase productivity on the ranch.
Lennie and George settle into the bunk house that all of the ranch hands share, and they meet Candy, an older man who is missing his hand. Shortly after this, they encounter Curley, the boss's son, who immediately begins antagonizing Lennie. When George asks Candy why Curley has a chip on his shoulder, Candy says that "He is alla time picking scraps with big guys. Kind of like he's mad at 'em because he ain't a big guy" (24). This insight into Curley’s personality explains his aggressive behavior throughout the novel. It also sets him up as a contrast to Lennie, who is a “big guy” (24) but has a mild nature.
After their foreboding meeting with Curley, Lennie and George encounter Curley's wife, who has what the workers describe as "the eye" (26). Many of these men call her a “tart.” She and Curley have only been married for a few weeks, yet she frequently stops in to talk with the workers, especially Slim, the jerkline skinner. George senses that Curley and his wife are trouble and warns Lennie to keep his distance from both of them.
That evening, Carlson, another ranch hand, complains about Candy’s elderly dog. He tells Candy to put the smelly, toothless dog out of its misery. While Candy initially refuses, a word from the wise and benign Slim changes his mind. Slim tells Candy: "Carl's right […] [t]hat dog ain't no good to himself. I wisht somebody'd shoot me if I got old an' a cripple" (43). Candy hesitantly agrees, even though, ironically, Candy himself is old and disabled. He cannot bring himself to shoot his pet, so Carlson offers to do it for him. This moment highlights society’s harsh views about individuals who are no longer able to work. The dog’s death also serves as another instance of foreshadowing. After Carlson kills the dog, Candy overhears George and Lennie's conversation about the little piece of land they hope to own. Candy offers to contribute all of his money if they will let him join them and work in the garden on their land.
Later that night, Curley comes into the bunk house and misinterprets Lennie's smile about the dream home as a personal affront. He attacks Lennie, who only fights back when George tells him to. Out of fear, Lennie grabs and crushes Curley’s hand. The men warn Curley that unless he wants to be embarrassed by the situation, he should tell people he caught his hand in a machine. Lennie is afraid that he has done something wrong, but George assures him everything is okay, and he will still be allowed to tend the rabbits on their farm. Lennie is reassured, and he goes to see the puppy that Slim had offered him earlier.
The following night all of the workers leave for a brothel they call "old Susy's" (49), and Lennie is left behind. Lennie visits his puppy in the barn. This barn is also occupied by Crooks, the disabled African-American stable hand who has worked on the ranch for years. Feeling as though his territory is being invaded, Crooks uses the opportunity to torment Lennie, suggesting that George might not come back. Lennie is immensely upset by this idea. Crooks calms Lennie down and tries to explain his own intense loneliness: "S'pose you didn't have nobody. S'pose you couldn't go into the bunk house and play rummy 'cause you was black. How'd you like that?" (69). Crooks’ speech underlines the extreme discrimination that he faces, and it also shows that he is isolated from the other men at the ranch. Lennie does not understand the significance of these comments, and he talks about his and George's plan to live together on their own small homestead. For a short span of time, Crooks imagines that he too might live on this piece of land and escape his life of inequality. But his new dream is quickly shattered after an altercation with Curley's wife, who degrades him for both his disability and his race. Crooks realizes that he could never live with the rest of the ranch hands and have the kind of life he desires.
The next afternoon, Lennie sits by himself in the barn. Next to him lies his puppy, now dead from Lennie's forceful grip. Fearing that George will not allow him to tend the rabbits on their farm, Lennie chastises himself and tries to decide what he should do. Then Curley's wife enters the barn. She tells Lennie about her regrets, most specifically that she married Curley rather than going into "movies" and "pitchers" (84). She reveals the details of her unhappy marriage, and she explains her desire for conversation to ease her loneliness. Noticing that Lennie is more focused on rabbits than her, she asks why he is so interested in them. He tells her that he likes to pet soft things, and she lets him feel her soft hair. When he starts to accidentally hurt her, Curley's wife screams. Overcome with fear, Lennie shakes her too hard and breaks her neck. Realizing he has done something terribly wrong, Lennie returns to the riverbed where George had warned him to go if he found himself in any trouble.
When George discovers what Lennie has done, he is forced to tell the other men. Candy, sensing that this incident changes their plans, seeks reassurance from George that the two of them can still work together to get a place. George, however, responds in the negative and confirms he never quite believed in the reality of the dream in the first place. Curley is furious and wants to kill Lennie himself. Knowing that Curley will kill Lennie in an inhumane manner, George is forced to make a decision out of the deep concern he has for his friend. Taking the same pistol that killed Candy's dog, George goes down to the riverbed to find Lennie. Lennie is relieved to see George and asks him to talk about the home they are going to own. George obliges, but tells Lennie to look out across the water. While Lennie is looking across the river bank and listening to George's story, George shoots him in the back of the head.
When the men reach George and Lennie, they assume George wrested the pistol from Lennie in order to kill him. The only person to show remorse and empathy is Slim, who tells George, "You hadda George. I swear you hadda" (102). Slim knew that George killed Lennie because he cared enough about him to not condemn him to Curley's cruelty or allow society to "[…] lock him up an' strap him down and put him in a cage" (92). Slim and George exit the scene to get a drink, leaving the rest of the men to watch them in bewilderment.