The story begins in May 1844 with Miranda Wells, the daughter of a humble farmer in Greenwich, Connecticut. Miranda's mother receives a letter from Nicholas Van Ryn, a rich relative and Patroon of a large manor called Dragonwyck near Hudson, New York. In the letter Van Ryn invites one of the Wells girls to Dragonwyck, to act as company for his daughter Katrine. After initial doubts, Miranda's parents allow her to go to Dragonwyck where she is instantly attracted to and intrigued by her rich, mysterious relative, Nicholas.
Not everyone welcomes Miranda to Dragonwyck. Nicholas' corpulent and lazy wife, Johanna, sees Miranda as a threat, and tries to keep her from her husband. Soon, Miranda encounters Doctor Jeff Turner, a skilled physician and a passionate anti-renter who believes that rich Patroons, like the Van Ryns, should give up their large estates. Van Ryn and Turner instantly dislike each other, and because of his views, Miranda is baffled when Nicholas asks the doctor to attend to his wife, who has a cold. However, while Dr Turner is at Dragonwyck, Johanna becomes violently ill and dies. As Dr Turner leaves, wondering what caused such a sudden death, Nicholas asks Miranda to marry him. She accepts.
Married life to Nicholas Van Ryn is far from what Miranda imagined. As the story moves on, Nicholas's true mental state and his thirst for power become evident. After their newborn son dies, the relationship between Miranda and her husband withers, and the bonds between Miranda and Dr Turner strengthen. Miranda and Dr Turner eventually discover that Nicholas poisoned his first wife, Johanna, with oleander. They confront him then try to escape, but Nicholas catches up with Miranda on a steamboat traveling down the Hudson River. The steamboat gets caught up in a race, catches fire, and crashes. Miranda is rescued by Nicholas, but he dies trying to save other passengers from the steamboat. After the ordeal, Miranda and Dr Turner marry, leaving the Hudson Valley area forever, for a new life in California.