On October 9, 2006, Kristi Rey and her husband Daniel are killed by her demon-possessed sister Katie, who then abducts Kristi's one-year-old son, Hunter. Text states that Katie and Hunter's whereabouts remained unknown.
Psychiatrist Dr. Miranda Grey (Halle Berry) works at a mental hospital and has a car accident after trying to avoid a girl (Kathleen Mackey) on a road during a stormy night while driving back home. She rushes to try to help the girl. The girl turns out to be a ghost and possesses Miranda's body by burning her after she extends her hand to the girl. Miranda loses consciousness. Miranda next wakes up in the very hospital she works for, but as a patient treated by her co-worker, Dr. Pete Graham (Robert Downey, Jr.). Drugged and confused, she remembers nothing of what happened after the car accident. To her horror, she learns that her husband Douglas (Charles S. Dutton) was brutally murdered and that she is the primary suspect. While Miranda copes with her new life in the hospital, the ghost uses her body to carry out messages (most noticeably, she carves the words "not alone" into Miranda's arm), which leads her former colleagues to believe Miranda is suicidal and is inflicting the wounds on herself.
The film opens with a parody of The Exorcist, during which a teenage girl, Megan Voorhees (Natasha Lyonne), becomes possessed by the spirit of Hugh Kane, the previous owner of the House. Megan's mother (Veronica Cartwright) calls in two priests, Father McFeely (James Woods) and Father Harris (Andy Richter), who visit the house. After Father McFeely pays a trip to the toilet, the men attempt to drive Hugh's ghost out, but the exorcism does not go as planned, resulting in a chain of projectile vomit and various instances of pedophilia. Finally, Father McFeely responds to an insult towards his mother by shooting Megan.
Twelve-year-old DJ Walters spies on his elderly neighbor, Horace Nebbercracker, who confiscates any item landing in his yard. DJ's parents leave town for a dentist convention, leaving him in the care of a babysitter, Elizabeth "Zee". DJ's best friend Charles "Chowder" visits him, but accidentally loses his basketball on Nebbercracker's lawn. DJ is caught by Nebbercracker while recovering it, who rages at him before apparently suffering a stroke and being taken away by an ambulance. That night, DJ receives mysterious phone calls from Nebbercracker's house with no one on the other end. DJ eavesdrops on Zee's boyfriend Bones, who tells Zee about losing his kite on Nebbercracker's lawn when he was young and that Nebbercracker supposedly ate his wife Constance. Later, Bones is driven out by Zee after he gets too fresh. When he leaves, he sees his kite in the doorway of Mr. Nebbercracker's house, but he and the kite are consumed, while retrieving it.
Mike Enslin (John Cusack) is a cynical, skeptical author who, after the death of his daughter Katie (Jasmine Jessica Anthony), writes books appraising supernatural events in which he has no belief. After his latest book, he receives an anonymous postcard depicting The Dolphin, a hotel on Lexington Avenue in New York City bearing the message, "Don't enter 1408." Viewing this as a challenge, Mike forces the hotel to allow him to book the room, referencing a law that any hotel room in New York can be requested as long as it meets safety standards. The hotel manager, Gerald Olin (Samuel L. Jackson) tries to dissuade Mike from checking into the room, explaining that 56 people have died in the room over the past 95 years, and that no one has lasted more than an hour inside it. Mike, who does not believe in the paranormal, insists on staying in the room, and asks Olin if he thinks it is haunted; Olin replies that it is "evil" rather than haunted.
Hands made of needles re-make a doll to resemble an 11-year-old Coraline Jones. A little later, Coraline and her family move from Pontiac, Michigan to the Pink Palace Apartments in Bandon, Oregon, which is also occupied by retired actresses Ms. Spink and Forcible, and eccentric Russian acrobat Mr. Bobinsky, who claims to be training a mouse circus. Coraline's parents work for a garden catalog and are often too busy to pay attention to her.
In an Edwardian-era English village, Crythin Gifford, three little girls are having a tea party with their dolls in an attic. They are smiling and having fun when they suddenly look at something in the corner. Then they stand up and walk trance-like to a window and jump to their deaths with blank faces.
Steven and Diane Freeling (Craig T. Nelson and JoBeth Williams) live a quiet life in an Orange County, California planned community called Cuesta Verde, where Steven is a successful real estate developer and Diane is a housewife who cares for their children Dana (Dominique Dunne), Robbie (Oliver Robins), and Carol Anne (Heather O'Rourke). Carol Anne awakens one night and begins conversing with the family's television set, which is transmitting static following a sign-off. The following night, while the Freelings sleep, Carol Anne fixates on the television set as it transmits static again. Suddenly, a hand of a white apparition blasts from the television screen and vanishes into the wall, triggering a violent earthquake in the process. As the shaking subsides, Carol Anne announces "They're here'.
In an unspecified Victorian-era village somewhere in Europe, Victor Van Dort (Johnny Depp), the son of nouveau riche fish merchants, and Victoria Everglot (Emily Watson), the neglected daughter of hateful aristocrats, are preparing for their arranged marriage, which will raise the social class of Victor's parents and restore the wealth of Victoria's penniless family. Both have concerns about marrying someone they do not know, but upon meeting for the first time, they fall for each other. After the shy Victor ruins the wedding rehearsal and is scolded by Pastor Galswells (Christopher Lee), he flees and practices his wedding vows in the nearby forest, placing the wedding ring on a nearby upturned tree root.
After celebrating at a drinking party with his close friends, Tun (Ananda Everingham), a photographer, and Jane (Natthaweeranuch Thongmee), get into a car accident. Jane hits a young woman. With much fear, Tun prohibits her from getting out of the car: they drive away, leaving the girl lying on the road.
A few years before the events of the first film, retired parapsychologist, Elise Rainier (Lin Shaye), reluctantly uses her spiritual ability to contact the spirit of Quinn Brenner's (Stefanie Scott) mother, Lillith, who died a year before. However, she urges Quinn not to make contact with her mother again after she senses that the spirit is not Lillith. Quinn begins to see a mysterious figure waving at her from a distance, and following her unsuccessful attempt to win an audition for a prestigious drama school, she is hit by a car and briefly flatlines before waking up with her leg cast.
In 1974, Ronald DeFeo, Jr. murdered his family at their house in Amityville, New York. He claimed that he was persuaded to kill them by voices he heard in the house. One year later, married couple George (Ryan Reynolds) and Kathy Lutz (Melissa George) move into the house along with the latter's three children from a previous marriage, Billy, Michael and Chelsea. The family soon begins experiencing paranormal events in the house. Chelsea (Chloë Grace Moretz) claims that she befriended a girl named Jodie, a name belonging to one of the murdered DeFeo children. One day the couple decide to go out, and they hire a babysitter to watch the 3 kids. When the babysitter, Lisa (Rachel Nichols), arrives they come to find out that she had previously been hired to babysit the DeFeos.
In the small town of Blithe Hollow, Massachusetts, Norman Babcock (Kodi Smit-McPhee) is an 11-year-old boy who speaks with the dead, including his late grandmother (Elaine Stritch) and various ghosts in town. Almost no one believes him and he is isolated emotionally from his family while being ridiculed by his peers. His friend, Neil Downe (Tucker Albrizzi), is an overweight boy who is bullied himself and finds in Norman a kindred spirit. During rehearsal of a school play commemorating the town's execution of a witch three centuries ago, Norman has a vision of the town's past in which he is pursued through the woods by townsfolk on a witch hunt. Afterward, the boys are confronted by his estranged and seemingly deranged uncle Mr. Prenderghast (John Goodman) who tells his nephew that he soon must take up his regular ritual to protect the town. Soon after this encounter, Prenderghast dies from a sudden stroke. During the official performance of the school play Norman has another vision, creating a public spectacle of himself which leads to his father (Jeff Garlin) grounding him. His mother (Leslie Mann) tells him that his father's stern manner is because he is afraid for him. The next day, Norman sees Prenderghast's spirit who tells him that the ritual must be performed with a certain book before sundown that day. Norman is at first reluctant to go because he is scared but his grandmother tells him it is all right to be scared as long as he does not let it change who he is. Norman sets off to retrieve the book from Prenderghast's house (having to take it from his corpse).
Young Debbie Galardi (Claire Beale) and Laine Morris (Afra Sophia Tully) play with a Ouija board in a flashback, where young Debbie tells Laine the rules of the board, the most important being not to play alone.