Fourteen-year-old Junior, a Spokane Indian boy, was “born with water on the brain” or hydrocephalus. This condition gave him a stutter, seizures, and a number of physical differences, such as a large head, that make him a frequent target for bullies on the reservation where he lives. As a result, Junior has spent a lot of his time alone, reading or drawing cartoons. He loves to draw, and thinks his cartoons pose his best chance of getting off the reservation and out of the poverty that has held his family and his tribe back for generations. He also loves spending time with his best friend, Rowdy, whose violent temper makes the other kids afraid of him. Rowdy always protects Junior, though, and the two boys share a special bond, telling each other their secrets and dreams.
On his first day of high school at Wellpinit (the school on the reservation), Junior is particularly excited for geometry class. But when the teacher, Mr. P, passes out textbooks, Junior realizes that the books are at least thirty years old. Suddenly furious that the reservation school is so poorly funded that it must use old and outdated books, Junior throws the textbook across the room—accidentally hitting Mr. P in the face and breaking his nose. As a result, Junior is suspended from school. Mr. P comes to visit him and tells Junior he forgives him, but advises him that he must leave the reservation. Otherwise, the culture of defeat, depression, and alcoholism on the reservation will force him to give up his dreams, just as his older sister Mary—who, Mr. P reveals, used to want to be a romance writer, but now spends all her time alone in the family’s basement—and the other adults in his life have done.
Because of Mr. P’s advice, Junior decides to transfer to the high school in Reardan, a wealthy white farm town twenty-two miles away. Junior’s parents support his decision, but warn him that most of the tribe will see him as a traitor. In particular, when Junior tells Rowdy he is changing schools and asks him to come along, Rowdy is angry and betrayed. He punches Junior in the face, screams that he hates him, and walks away. Junior is heartbroken, realizing that his best friend has become his worst enemy.
At the Reardan school, Junior is the only Indian besides the racist mascot, and he feels deeply alienated from the white students, who either ignore him or call him names. He also feels like his identity is divided between Reardan and the reservation, particularly because the white teachers call him by his given name, Arnold, instead of Junior. Gradually, though, Junior makes friends with some of his new classmates, including Gordy, a “genius” who teaches him how to really read books; Penelope, a beautiful, popular blond girl who becomes Junior’s “semi-girlfriend” after he discovers her eating disorder and lets her cry on his shoulder; and Roger, a star athlete who encourages Junior to join the basketball team. Much to his surprise, Junior excels on the team, impressing Coach with his shooting skills and his commitment. In the team’s first game against Wellpinit, Rowdy gives Junior a concussion, sparking a thirst for revenge that drives Junior to humiliate him in turn later in the season—only to realize, after a crushing Reardan victory, that perhaps he shouldn’t be so proud given Reardan’s advantages.
Junior’s first year at Reardan is also filled with many deaths on the rez, all of them related to alcohol. First, his beloved grandmother is killed by a drunk driver. Weeks later, his father’s best friend Eugene is shot during a drunken argument. Then, right after Reardan’s victory over Wellpinit, Mary dies when her trailer home burns down after a wild party. Junior is devastated, and blames himself for her death—she moved to Montana right after he decided to leave the reservation, and might never have left home if he hadn’t done it first. However, the sympathy from his classmates at Reardan makes him realize that he matters to them now, just as they matter to him. Later, when Junior and his parents go to the cemetery to care for Mary, Eugene, and Grandmother’s graves, he comes to a realization that he will be able to leave the reservation, and although he will be lonely, he won’t be completely alone—he actually can and will always be a member of many tribes, from the tribe of cartoonists to the tribe of people who have left their homes.
Shortly after the last day of school, Rowdy comes to see Junior and invites him to play basketball. Rowdy doesn’t apologize for everything he’s said and done, but he does tell Junior that he always knew he would leave the reservation, and that he looks forward to Junior’s travels and is happy for him. Junior hopes and prays that someday Rowdy and the rest of his tribe will forgive him for leaving—and that he will someday be able to forgive himself. The novel ends as Junior and Rowdy play a one-on-one game of basketball into the night, without keeping score.