The film begins with an old woman trying to open a strange box. She turns on old classic music and grabs holy water and a hammer. Before she is able to destroy the box, she is thrown violently around the room by an unseen force. When her son enters, she is unconscious on the floor.
Next, the audience is introduced to newly divorced couple Clyde (Jeffrey Dean Morgan) and Stephanie Brenek (Kyra Sedgwick). They have two children, Em (Natasha Calis) and Hannah (Madison Davenport). Clyde introduces his daughters to his new house.
At a yard sale with Clyde and Hannah, Em becomes intrigued by an old box which has Hebrew inscriptions engraved on it. Clyde agrees to buy the box for her. When Em walks around the yard carrying the box, she discovers the old woman lying in bed, covered in bandages. Upon seeing the box, the woman slams her hand against the window, screaming,and jumping until her nurse closes the blinds.
Em asks Clyde to open the box, but he is unable to and concludes it is not meant to be opened. Em keeps it in her bedroom and that night, begins to hear whispering coming from it. She opens it and finds a tooth, a corpse of a moth, and a ring, which she begins to wear.
Em becomes solitary and spends her spare time staring at the box. Her behavior grows increasingly sinister, to the point where she stabs her father in the hand with a fork. The house later becomes infested with moths, mainly clustered in Em's room. One night while Em is in the bathroom, she starts to gag. She uses a flashlight and points it into her mouth. After a few seconds, a hand is seen crawling up from the back of her mouth. Em is startled, but doesn't say anything and goes back to bed.
At school, one of Em's classmates discovers the box and begins to antagonize her about it. She screams at him to give the box back and strikes him multiple times before being restrained by her teacher. Clyde and Stephanie are summoned to a meeting with Em's principal and teacher, where they discuss Em's growing violence and how she is becoming increasingly antisocial.
Em's teacher recommends that Em spend time away from the box, so it is left in the classroom. Later that night, curious about the noises emanating from the box, the teacher tries to open it, but dies when a malevolent force throws her out a window.
Em tells Clyde about an invisible woman who lives in her box and says Em is "special". Alarmed by her behavior, Clyde attempts to dispose of the box. Clyde returns home and finds Em, crying, asking what he has done with the box. When Clyde refuses to tell her, an unseen force slaps Em, making it seem as if Clyde is abusing her. Em runs away, finds the box, and begins to converse with the dybbuk. Suddenly, moths fly out of the box and into Em's mouth. Em faints and Clyde carries her unconscious body back to his house, where the police and Stephanie wait to take her away from him. Clyde returns to pick up the box.
Clyde takes the box to a professor at the university who tells him it is a dybbuk box that dates back to the 1920s; it was used to contain a dislocated spirit, an ancient Jewish evil or demon. Clyde sneaks into Stephanie's house, enters Em's room and begins to read the Torah to her. Em stares at him blankly, and a force hurls the Torah across the room. Stephanie then comes home, causing him to retreat.
Clyde then travels to a Hasidic community in Brooklyn, and learns from a Jew named Tzadok (Matisyahu) that the possession has three main stages; in the third stage the dybbuk latches onto the host, becoming one entity with it. The only way to defeat the dybbuk is to lock it back into the box via a forced ritual. While further examining the box, Tzadok discovers the demon's name is Abyzou, which he explains is the "taker of children".
Later that evening, Em violently attacks her mother when Stephanie discovers her gorging herself like an animal out of the refrigerator. Stephanie's boyfriend Brett suggests that Em be examined by a psychologist.
The next morning, Brett prepares to take Em to the psychologist. However, when Em stares malevolently at Brett, his mouth begins gushing blood and his teeth begin falling out, causing him to drive away frantically. Em then has a seizure on the front lawn and is taken to the hospital for an MRI. During the procedure, the lights begin to flicker and Stephanie and Hannah are horrified when they see the dybbuk's face in the images, next to Em's heart.
Stephanie then realizes that Em is possessed. Clyde and Tzadok join the rest of the family at the hospital and attempt to conduct an exorcism. After Em breaks free and attacks Tzadok, she escapes to the morgue with Clyde in pursuit. Clyde survives Em's attack but is now possessed. Tzadok performs an exorcism which is successful; the dybbuk crawls out of Clyde and back into the box.
The family is reunited, with Clyde and Stephanie's love rekindled. Tzadok drives away with the box in Clyde's vehicle. Just after calling Clyde, the car is suddenly hit by a truck, apparently killing him. The box is then seen, having landed several feet from the wreckage.