Jean Louise (Scout) Finch and her brother Jem spend their time playing with an orphan friend Dill, who only comes for the summer. Much of their time is spent trying to see Boo Radley, the shut in who lives down the street. Dill leaves at the end of the summer and Scout goes to school for the first time, where her ability to read frustrates her teacher. On their way home from school, the siblings periodically find items (chewing gum, coins, a watch) left in the hollow of an Oak tree outside the Radley house (Boo's doing - a fact which is confirmed at the end of the book).

It soon becomes clear that Atticus (an attorney) is defending a black man in a case that has the town upset with the Finch's. Scout gets in a fight at school, after which Atticus asks her to be strong during this time. Tom Robinson, a pleasant, gentle man, has been accused of raping Mayella Ewell. The Ewell family is not well-respected, and they live near the county dump where they scrounge for food and supplies. However, in spite of evidence that would exonerate Tom (he has a crippled left arm, and the blows that struck Mayella came from the left side) the jury still convicts him. (In fact, the book makes it evident that Mayella actually made advances on Tom, who rejected them, but was forced to flee when Mayella's father arrived.) While Atticus believes they have a good chance of having the ruling overturned on appeal, Tom attempts to escape one night from prison, where he is shot and killed.

Though the trial is over and Tom is dead, Bob Ewell (Mayella's father) still feels shamed from the trial (where is being left-handed incriminated him to have actually inflicted the beating). He threatens Atticus, harasses Tom's widow, and breaks into the Judge's house. Atticus thinks this is the extent of what he will try, but one night he attacks Jem and Scout on their way back from a pageant at the school. During the fight, Bob breaks Jem's arm, but he is killed by Boo Radley. Heck Tate (the sheriff), however, spins the story that Bob fell on his own kitchen knife, killing him, in order to protect Boo from the attention his protection of Jem and Scout would cause. The book ends with Scout sleepily reflecting to her father that, while they were scared of Boo in the end, he turned out to be "real nice".