In a Bronx Catholic school in 1964, Sister Aloysius Beauvier, the school’s strict principal, becomes suspicious when Father Flynn, a beloved and progressive priest, takes a particular interest in Donald Miller, the school's first African American student. Sister Aloysius harbors a deep mistrust of Flynn’s modern methods and easy camaraderie with the students. After observing a private meeting between Father Flynn and Donald, and noticing Donald’s upset demeanor and the smell of alcohol on his breath, Sister Aloysius confides her suspicions to Sister James, a young and naive teacher who had noticed the boy's strange behavior but wished to think the best of Flynn. Sister James is torn between her admiration for Flynn and her loyalty to Sister Aloysius.

Driven by a duty to protect her students and a rigid certainty in her moral judgment, Sister Aloysius embarks on a personal crusade to uncover the truth and to have Father Flynn removed from the school, despite having no evidence but her conviction. Her determination leads to a confrontational meeting with Flynn, where she demands his resignation. The conflict escalates, drawing in the boy’s mother, Mrs. Miller, who reveals complex perspectives on the situation that confound the issue further. Sister Aloysius must navigate the murky waters of doubt, faith, and morality, pushing the limits of her authority within the hierarchical confines of the church.