An art gallery owner, Susan Morrow, leads a visually luxurious but emotionally hollow life with her husband in Los Angeles. Out of the blue, she receives a manuscript from her ex-husband, Edward Sheffield, whom she hasn't heard from in years. The novel, dedicated to her, is titled "Nocturnal Animals," which was Susan's nickname for Edward. As Susan begins reading the gripping and violent story, it starts to consume her thoughts and awakens memories and feelings about her past relationship with Edward, including their youthful romance and eventual heartbreaking separation.

Within the manuscript, the novel's narrative follows Tony Hastings, a family man who, while on a road trip through West Texas with his wife and daughter, encounters a gang of menacing troublemakers led by the unhinged Ray Marcus. This chance encounter leads to a nightmarish sequence of events that turns Tony’s life upside down. As he seeks justice for the unspeakable crime committed against his family, he receives assistance from a pragmatic and near-retirement detective, Bobby Andes. Meanwhile, Susan becomes increasingly disturbed by the novel's contents, which seem to be a symbolic revenge tale, and begins to draw parallels between the story and her personal life, forcing her to confront her own past decisions and their consequences.