Like so many white men during the Great Depression, George Milton is without a home and a stable job. He and another man named Lennie, the nephew of Aunt Clara, whom George has promised to care for, are the disposessed, the "bindle stiffs." As Lennie is mentally challenged, George must act as a big brother and counsel and direct Lennie. For instance, in Chapter 1 he tells Lennie he cannot play with mice since he kills them. And, because Lennie has already been responsible for their having to flee from a town called Weed, George advises Lennie to remember the pond and the bushes where they camp for the night.
"Lennie--if you jus' happen to get in trouble like you always done before, I want you to come right her an' hide in the brush."
Since he and Lennie travel together, a condition unusual for the alienated bindle stiffs, many men are mistrustful of them at first. So, George has to explain their relationship. Sometimes he lies, telling the boss, for example, that Lennie is his cousin. Soon, George becomes friendly with Slim, who has "God-like eyes" and is sympathetic when George talks. But, later on, when the son of the boss, Curley, stands in the bunkhouse doorway, George understands the threat that this young man presents. However, when Curley punches Lennie repeatedly, George tells Lennie to "get him" and the big man severely injures Curley's hand. Recognizing Curley's wife as a threat, as well, George tells Lennie to stay away from her.
However, Curley's wife stations herself wherever the men are and Lennie encounters her at the barn where he has gone to pet his puppy while George has gone into Soledad. Unfortunately, while he has been gone, George discovers that Lennie is missing; Candy informs him of the tragedy. Now, George realizes that Lennie will be put away into an institution of some kind. Knowing that Lennie cannot bear such a life, George goes to the clearing and mercifully shoots Lennie to spare him a miserable life.