In the early morning hours on November 13, 1974, Ronald DeFeo Jr. murders his entire family with a shotgun at their home in Amityville, New York.

One year later, George and Kathy Lutz, a young married couple, move into the property. George appears not to be strong of faith, but Kathy is a Catholic in name at least. She has three children from her prior marriage: Greg, Matt, and Amy. The couple turn to Father Delaney to quickly bless the home, but Delaney encounters troubles in trying to bless the home, including a room full of flies, out of season; violent stomach sickness; and later, blisters on his palm when trying to make a phone call to Kathy at their home. The experience eventually stops when a door is opened, then a voice whispers "get out". He rushes out of the house when the voice yells at him, and he decides to continue helping the Lutz family. Delaney is later involved in a car accident resulting from mysterious malfunctions, and he becomes frustrated at the lack of support from his superiors in the diocese. He ultimately appears to lose faith, becoming blind and having a breakdown.

Kathy's aunt, a nun, comes by the house one afternoon, but becomes violently ill. George begins to be more sullen and angry over perceived cold in the house, and obsesses with splitting logs and keeping the fireplace stoked. Before Kathy's brother's engagement party one night, $1,500 to be used for the caterer inexplicably goes missing in the house. Meanwhile, the babysitter watching Amy for the evening is locked inside a bedroom closet by an unseen force. Further unexplained incidents occur when one of the two boys suffers a crushed hand when a sash window falls on it, and Amy having an imaginary friend, Jody, who seems to be of a malevolent nature. Kathy catches a glimpse of two red, swine-like eyes outside the daughter's second-story bedroom window. Even the family dog, Harry, scratches obsessively (causing his paws to bleed) at a brick wall in the basement.

George's land surveying business begins to suffer with his lack of attendance, and his business partner, Jeff, grows concerned. Jeff's wife, Carolyn, very sensitive to the paranormal, is both repulsed and intrigued by the things she feels when at the house. While in the basement of the house, Carolyn begins demolishing a wall with a hammer, revealing a small room behind the wall. Discovering the damage, George takes down the rest of the wall, observing a small room with red walls. Carolyn, in terror, shrieks that they have found "the passage... to hell!" – only her voice now sounds like Father Delaney's voice.

Throughout the strange incidents, Kathy observes George's persistent waking up at 3:15 a.m., feeling he must go check on the boathouse. She also has nightmares, in which she is given details about the killings of the home's prior family. Research at the library and county records office suggest that the house is built atop a Shinnecock burial ground and that a known Satanic worshipper named John Ketchum had once lived on the land. She also discovers the news clippings about the DeFeo murders and notices Ronald DeFeo's striking resemblance to George.

Finally, the paranormal events culminate one stormy night. Blood oozes from the walls and down the staircase; Jody, appearing as a large, red-eyed pig, is seen through a window; and George attempts to kill the children with an axe, but regains his wits after Kathy disrupts him. After falling through the basement stairs into a pit of black sludge while rescuing Harry, George and the rest of the family drive away, abandoning their home and belongings. A final intertitle reads: "George and Kathleen Lutz and their family never reclaimed their house or their personal belongings. Today they live in another state."