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QB is set in Appalachian America where a working-class man and his wife, Albert and Louise Pickett, experience the birth of their intersex child. The parents raise the child as a girl named May, but social conditioning is overpowered by biology: May insists that "she" is a boy. After an embarrassing rebellion, Albert and Louise send May to live with Isabelle in Ohio. Isabelle and her new husband, Coach Koontz, raise the child as a boy named Mayson. Mayson develops into a dominant football player under the guidance of Coach Koontz. In addition to being the top-rated quarterback in the state, jealousy from his brother and father further complicate the pressures of high school life and what it means to be a man without a fully developed penis. Mayson's secret is discovered during freshman hazing, and his father leaks the story to the press. What ensues is a media storm over the high school state football championship: Mayson leading one team, his brother the other.