A man enters the Dallas, Texas FBI office one rainy night, and introduces himself as Fenton Meiks (Matthew McConaughey). He wants to speak to Agent Doyle (Powers Boothe) about his belief that his brother Adam (Levi Kreis) is the notorious "God's Hand" serial killer.
Fenton explains that he is only coming forward now because earlier that day Adam had called him to say that he cannot stop the "demons" because there are too many, and killed himself. Fenton says that he stole Adam's body to bury it at the Thurman Rose Garden, according to a promise the brothers made many years ago. Agent Doyle continues to be skeptical, and Fenton unfolds through flashback the story of their childhood with their widowed father (Bill Paxton).
When Fenton and Adam were young boys, their father tells them that he had been tasked by God to root out and destroy demons whose names were to be provided for him by an angel. Special tools have been given to aid him: gloves to protect his hands, a lead pipe to knock them unconscious, and an axe named 'Otis' to destroy them with. At this news, Fenton mentally shuts down, refusing to believe their father will really kill people, but Adam quickly believes their father to be doing God's work.
Their father captures his first victim, a woman named Cynthia Harbridge (Cynthia Ettinger). When he touches her, he claims he can "see" the sins she has committed, and has no guilt when he uses Otis to "destroy" her. Both Fenton and Adam are forced to witness this act; Fenton is traumatized, but Adam claims he can "see" the woman's sins as well. Her body is buried outdoors in the Thurman Rose Garden which is next to the Meiks house. Fenton tries to explain to Adam that their father has gone insane, but Adam continues to believe him, leading Fenton to conclude that his younger brother has been successfully brainwashed.
After the third victim is captured, Fenton decides to inform the town Sheriff (Luke Askew). When Sheriff Smalls arrives, Fenton's father kills him with the axe. Unlike the previous acts, the father says that this one is "murder" and blames Fenton for forcing him to commit it. The father confesses that the angel told him that Fenton is also a demon and has to be killed. Fenton begs for mercy, and his father locks him in the cellar. After being nearly starved to death, Fenton has a "vision of God" and is let out.
Fenton, Adam and their father track down another supposed demon and capture him. Fenton is given Otis to chop the man's head off, but he instead kills his own father. Fenton moves to release the captured man, but Adam grabs the axe and kills the "demon", apparently having taken over their father's work.
Back in the present, Agent Doyle is convinced that Fenton's story has weight, and drives Fenton to the Thurman Rose Garden, where Adam would surely have buried his victims. Once they arrive, it is revealed that the adult man who has been calling himself "Fenton" is really Adam. However, the "God's Hand" killer is the real Fenton, who kept the bodies of his victims as trophies in his house basement. Fenton used the "God's Hand" nickname to lure Adam out, knowing that his brother would have to kill him one day so to fulfill the task their father could not do. Fenton has been buried in the Rose Garden, along with the many demons Adam had "destroyed" over the years.
Adam also explains that he lured Agent Doyle there because he was on God's list. When Adam touches Doyle's hand, a vision is revealed of Doyle killing his own mother in cold blood. Adam picks up Otis from the undergrowth and destroys Agent Doyle, burying him in the Rose Garden.
The next day following Agent Doyle's disappearance, agents at the bureau frantically try to find the "Fenton Meiks" he left the building with. Agent Hull, who had met Adam-as-Fenton the previous night cannot remember the man's face, and all security footage showing Adam's face has been distorted. Eventually the FBI storm the real Fenton Meiks' house, and find evidence of his killings, along with Agent Doyle's FBI badge.
Agent Hull visits the local Sheriff's office, and the Sheriff is revealed to be Adam Meiks. Agent Hull does not recognize him, and explains that his visit is to inform him about his brother's death and killing spree. They shake hands, during which Adam holds a moment too long only to tell the agent, "You're a good man."
