Keller Dover (Hugh Jackman) and his son Ralph are hunting deer, Ralph drops a buck as Keller recites the Lord`s Prayer, then smiles approvingly at the teen. On the drive home Keller tells his son to always ``be ready``.
An old RV drives past the Dover house. Later they talk about the family finances, Ralph wonders why they don't rent out the grandfather's old apartment, Keller says it is in too poor condition.
The family, Keller, his wife Grace, son and daughter walk to a neighbor`s house for Thanksgiving dinner with their friends the Birches. The families have a good time together. While the adults cook the kids go out, Anna Dover jumps on the old RV parked by the curb, they realize someone is inside and return back to the Birch house. Franklin Birch (Terrence Howard) is an affable man and plays a bad trumpet. After dinner, the younger6-year old daughters leave to go back to Anna's house to get her safety whistle she is supposed to carry at all times.
Some time later Keller realizes the girls haven`t returned and that the teens hadn`t escorted the two young ones. Keller searches his own home to no avail. Ralph returns from looking also and mentions the RV from earlier.
Detective Loki (Jake Gyllenhaal) has Chinese food alone and chats with the waitress. His phone buzzes.
After a police hunt, the white RV is found parked outside a gas station next to a wooded area. When Det. Loki, who heads the case, goes to confront the RV's driver, Alex Jones (Paul Dano), Alex panics, tries to speed away but crashes into the trees.
Alex is taken in for questioning, but it is found that he has the IQ of a 10-year-old and rarely speaks. Detective Loki goes to see Alex's aunt, Holly Jones (Melissa Leo), who raised him with his uncle after his parents died when he was six. Alex's uncle left the home a couple years ago after a domestic dispute with his aunt. Alex spends most nights sleeping in the RV and does not have many things. The RV shows no forensic evidence indicating the girls were forcibly taken into or struggled inside the RV, and Alex's low intelligence means he couldn't have covered up such evidence.
At night many volunteers search the woods calling for the girls. Loki comes to the Birch house and gets better photos of their daughter. At the Dovers, Loki tells Grace they passed the lie detector tests they did, he asks if there was a reason the girls ran away. Grace is weepy and says the girls were happy, Loki vows to find the girl. He greets Keller, who seems sure it must be the RV driver.
Loki tells the Dovers the evidence against Alex Jones is weak and tries to calm him down. The
polygraph tests of him prove inconclusive due to his low IQ, and he repeatedly denies ever having seen the children. As the police are unable to find evidence against Alex, he will be released in two days. Loki asks his Capt to hold Alex longer but the senior refuses. Loki updates him on the search.
Loki interviews sex offenders within a 10 mile radius of the girls' homes. Loki discovers that a Father Patrick Dunn has a bound and mummified body in a barricaded basement. The body is wearing a circular medallion with a maze design. Father Dunn claims that he did not know who the man was, but that in confession the man talked about killing sixteen children and also admitted to having a marital dispute. Father Dunn confesses that he convinced the man to come to his house, where he killed him "to save the children" and is arrested for murder.
The search of the woods and river continues. Keller has found out when Alex is being released and attacks him in the police parking lot. He hears Alex say "They didn`t cry until I left them." Though no one is close enough to hear this to corroborate, but Keller takes this as proof that Alex took the girls.
Captain O`Malley lets Dover off with a warning and sends him home after a brief talk with Loki.
At the Jones house Loki interviews Alex and Holly again about the parking lot incident. He threatens to send the aunt to jail if Alex is not honest. He then leaves and stands in front of an old car.
Grace is distraught, Keller gives her a sedative to help her sleep. He tells his son to be brave and grownup and look after his mother, then leaves the house.
That night, Keller abducts Alex at gunpoint while walking his dog, and imprisons him in his father's old abandoned, run-down apartment house. The next morning He shows Franklin Birch, the captured man bound with duct tape; Birch is horrified as Keller starts questioning.
Detective Loki researches past unsolved missing children's cases. One is Barry Milland, a boy missing since age 6, 26 years ago. An interview with his mother shows her playing and replaying a VHS tape of him just before his abduction. He interviews Father Dunn again, in custody. Dunn says the man abducted kids in daylight and took more than one at a time. Loki feels the info is useless. The body is not identified by DNA or missing persons' reports.
Keller repeatedly beats Alex for information, enraged that the man won't say what he did with the girls.
During a candlelight vigil for the missing girls, Detective Loki notices a man acting suspicious, but loses him in a chase.
That evening Birch watches the news item on TV about the man, they show a sketch and the next day he goes to see Dover to tell him there is another possible man.
Loki and his boss, Capt. O`Malley argue about resources for the continuing hunt.
Loki watches the video of Alex' interview, he gets a phone call tip. A discount store clerk recognizes him and states that he comes in from time to time to examine children's mannequins and buy children's clothing. The clerk gives Loki the man's license plate to track him down.
Franklin is overcome with guilt and tells his wife Nancy (Viola Davis) what they have done and brings her to see Keller. Dover brings her to the apartment where Alex is brutally beaten, bloody and tied to the bathroom floor. Shocked, she unties Alex and tries to talk to him nicely, but he attempts to escape. Dover grabs him. Tied again, Alex watches as Dover starts building something from plywood.
Later, Dover then brings the Birches back to the apartment. Keller has built an enclosure around the bath tub in which he nails Alex. It is devoid of light except for a small PVC tube talk-hole. Keller says otherwise he would kill the man, and challenges the Birches to let him go. Franklin says it has to stop but does nothing when Nancy tells him to think of Joy.
While the Birches teen daughter Eliza is in the bath the strange man walks silently in their house. Later the hooded man enters the Dovers house, Grace hears something and jumps out of bed. She finds an open window and believes Anna had come back. Detective Loki arrives writes down her statement of someone coming in through the window. Grace shows him the basement, Kellers well organized workshop. Loki sees a bag of lye and asks Grace where Keller is, she says he is out looking for their daughter.
In a pouring rain, Loki follows Dover, but is "made", Dover turns back from the apartment and goes to a nearby liquor store instead.Loki wonders what he was doing in the area. Dover approaches with a bottle , and asks why he is being followed. He says this is first drink in nine years. Loki urges Dover to take care of himself and his wife. It has been six days, Dover gets very angry, but then goes home to sleep. He dreams he sees Anna.
Loki works at his computer. He reads an old news archive of a suicide, which occurred at 234 Campobello, the same location Dover was near.
The next day Keller tortures Alex with alternating scalding and freezing water from the showerhead. Alex tries to talk but Dover just wants to hear where the girls are. Dover kneels to pray. Loki arrives at the boarded up building and enters the ground floor. He finds Dover pretending to sleep on the floor. Dover gives the policeman a short tour of the ramshackle building, then his cell phone rings with the store clerk, the intruder has been spotted. Loki leaves quickly.
Loki confronts Taylor at his home, notices he is strange and forcibly handcuffs hime. He calls it in and searches the house. The walls are covered in drawings of intricate mazes. In a back room, locked boxes are filled with maze books, venomous snakes, and bloody children's clothing. At the police station both the Dovers and Birches identify clothing belonging to their children from the crates, and Taylor confesses to killing them.
Taylor is weeping while handcuffed in the interrogation room and draws a maze. Loki watches for awhile then enters. He loses control and beats Taylor during questioning, other cops rush in. Taylor manages to grab one of the officers' gun from his belt and commits suicide.
Back at the apartment prison Keller sits and recites the Lord`s Prayer.
At the police station the Captain chides Loki for the death.
Keller is drinking as Alex finally talks and mentions something about finding the girls in a maze.
Keller goes to the Jones home to "apologize" to Holly for attacking Alex at the police station. She invites him in and tells Dover her son died of cancer and commiserates. Keller says he dreams of Anna in a maze. Holly also mentions her husband kept snakes. A newspaper headline grabs Dover`s attention, the report of Taylor's suicide.
Capt. O`Malley tries to tell Loki to get over it, you can`t win them all and to find a girlfriend. Loki goes to his workstation in a rage. In a pile of photos he notices a picture of a maze similar to the one Taylor was drawing. Back at Taylor`s house another cop reveals the blood on the children's clothes is later found to be pig's blood. Taylor is now felt to be a fake killer copying a book titled "The Invisible Man" which prominently features mazes, especially a circular maze (seen in the "O" in the "Prisoners" logo and as the maze medallion worn by the body in Father Dunn's basement) which Taylor was drawing while in custody. Loki can`t figure out how Taylor had the missing girl`s clothes.
He returns to the Dover`s house and finds a small sock in the bushes. Someone calls Grace and she excitedly finds Keller.
Joy Birch has been found wandering, drugged and is hospitalized. Keller tries to question the young girl. Anna remains missing. In her drugged state, Joy rambles that Keller was there, giving the people around her the impression that Keller is somehow in on it. Keller rushes off as Loki chases him in the hospital, then to a car chase outside. Loki loses Keller, but heads towards Keller's apartment building and discovers the imprisoned Alex.
Keller has gone to Holly's, with a tool belt and offering to do some penance for his behaviour. Holly once again is friendly and invites him in for a tea. Keller confronts her about the girls but the woman holds him at gunpoint and forces him to put on handcuffs and consume the same sedative used to drug Anna and Joy. At gubnpoint she directs him to an old car outside . She reveals that she and her husband had been religious people, like Keller, until their son died of cancer at a young age. Holly and her husband decided to make a war on God by making children disappear without a trace to turn their parents into demons, as evidenced by what Keller had become. Her husband then disappeared and she ``does what she can``. She orders Keller to drive slowly, and tells him Alex never touched the girls. The car had been covering a pit, Holly tries to force him in and shoots him in the leg, he drops into the hole. She closes the lid and parks the car again over the lid.
The Capt. tells Loki to go to Holly`s and let her know about Alex.
With a small flashlight Keller explores his dungeon. He finds his daughter's whistle, and prays for Anna`s safety.
Loki arrives. Holly goes to a locked room to get Anna. Loki enters the house and sees an old photo of Alex and his RV. He then creeps toward a noise. Holly is injecting the girl with a syringe and Loki demands she stop, they both fire their weapons. Holly is killed and a wounded,bloody Loki races the girl to the hospital.
The next morning a bandaged Loki reads a newspaper, the headline says Barry Milland, aka Alex Jones has been reunited with his family. Grace comes in and says Anna will be fine, the Birches and Dovers leave. Grace says Keller still hasn`t contacted her, she realizes Keller will be going to jail when caught.
At night, at the Jones house the CSI techs say they have found some dead snakes but the ground is frozen. They leave for the night. Loki stays behind for a while then hears a whistle.