The basic plot of the book can be summarized in three points.
First, George and Lennie are two friends who are trying to make it during the depression. They are migrant workers. George is a small and clever man; Lennie is a big and mentally delayed man. The world is a cruel place and so both men have a hard time. They only have each other.
Second, George and Lennie leave from one place to find employment in another. When they arrive, all seems well, but the boss's son Curley has it out for Lennie. Eventually, Lennie beats him up, but Curley's wife is flirtatious and lonely. As she develops a friendship with Lennie, Lennie accidentally kills her. When this happens, the men on the ranch hunt Lennie to kill him—probably brutally.
Third, when George finds out about all of this, he finds Lennie first to do the most merciful thing. George finds Lennie and as George paints a picture with words about their future utopia, he shoots him in the head.