Vincent Price plays Joseph Curwen, a man accused of being a warlock. The townspeople of the village of Arkham tied him to a tree and burned him. Joseph Curwen cursed the village people and vowed to return.

110 years later, the great-great grandson of Joseph Curwen, Charles Dexter Ward, also played by Vincent Price, along with his wife, Ann Ward, played by Debra Paget, returns to the town. Charles Dexter Ward had recently acquired his family home and upon his and his wife's arrival, they meet Simon the caretaker, played by Lon Chaney Jr.

Charles and Ann decided to have a walk around town only to be greeted or should I say "not greeted" by some townspeople who looked deformed and weren't very happy to see Charles and Ann. Befriended by the local doctor, Dr. Willet, who walks Charles and Ann to their home and joins them for dinner, he tells the Wards (Charles and Ann) the story about Joseph Curwen. Dr. Willet elaborates about Joseph Curwen's practices of witchcraft and unholy experiments on humans, which cause the mutations on some of the townspeople and cause them to fear the Wards.

Feeling unwelcome, the Wards decided to leave Arkham only to have their decision changed by Simon the caretaker; so the Wards spend the night at the family home. Upon looking at the portrait of Joseph Curwen, Charles Dexter Ward's body is possessed by his great-great grandfather. Simon the caretaker is actually a friend of Joseph Curwen's past and Simon along with a third friend named Jabez are reunited with Joseph Curwen. The three men want to unlock the secrets of the book of Necronomicon and unleash evil beings upon the world.

Ann Ward is frightened by her husband's odd behavior and strange mood swings. Feeling frustrated by Ann's refusal to fulfill her wifely duties, the possessed Charles Ward along with Simon and Jabez , bring Hester, a former servant and mistress of Joseph Curwen's past, back to life.

The possessed Charles commit a series of murders as an act of revenge against the descendants of the townspeople who burned Joseph Curwen 110 years ago. Ann disturbed by the strange sounds at night, decides to look around the home. Unfortunately, she finds "Charles" along with Simon, Jabez and Hester trying to bring back the "evil beings" again. They give Ann a first hand look by making a sacrifice or rather a mating partner with these "evil beings".