In rural Virginia, Sheriff Sheldon arrives at a bizarre crime scene inside a suburban home where an entire family has been brutally murdered. In the basement, buried in the dirt, deputies unearth the pristine, unblemished corpse of an unidentified young woman with no signs of external trauma. Needing a cause of death for the morning press conference, the sheriff brings the Jane Doe to Tommy Tilden and his son Austin, who operate the county morgue and crematorium out of their basement.

Austin postpones a movie date with his girlfriend Emma to help his father finish the late-night assignment. They begin with an external examination and immediately uncover impossible contradictions. Jane Doe's wrists and ankles are shattered internally with no skin bruising, her tongue was crudely severed, her waist is unnaturally compressed as if bound by corsets, and her eyes have turned cloudy gray as though dead for days, yet her body is completely fresh and bleeds freely like a fresh kill.

Moving to the internal autopsy, the mystery deepens into a nightmare. Tommy cuts open her chest and discovers her lungs are completely blackened from severe third-degree burns, her heart is scarred, and her internal organs show extensive cutting trauma with no corresponding external marks. Inside her stomach, they find jimsonweed—a paralytic flower native to the Northeast—and a rolled-up square of linen cloth decorated with ancient symbols and Roman numerals.

Outside, a severe storm hits the town, blowing out the power grid and knocking out the radio, which keeps resetting to an eerie retro pop song, "Open Up Your Heart (And Let the Sunshine In)." The generators fail, plunging the morgue into darkness. When Tommy investigates the hallway, he finds the refrigerated storage drawers thrown open and the other stored corpses missing. Heavy footsteps and the chime of a bell—tied to corpses' toes in case they wake—echo through the dark corridors.

Austin and Tommy try to flee, but the elevator is dead and the storm cellar doors are blocked by fallen trees. After a horrifying hallucination leads Tommy to accidentally kill Emma with an axe when she returns to the morgue, father and son realize the corpse is not a victim of a modern homicide. The symbols on the linen cloth match Leviticus 20:27, an Old Testament verse condemning witches. Jane Doe was a 17th-century woman accused during the Salem witch trials. The brutal tortures used by the Puritan magistrates did not kill a witch; their atrocities transformed an innocent woman into an immortal, vengeful entity that cannot die.

Realizing Jane Doe is telepathically retaliating for every incision they made, Tommy offers his own life to appease her wrath and save his son. The entity accepts, supernaturally breaking Tommy's limbs, burning his lungs, and transferring her internal trauma onto him. Tommy begs Austin to end his misery, and Austin tearfully stabs his father in the heart. Left alone in silence, Austin hears Sheriff Sheldon's voice outside the elevator, only to realize too late that it is another hallucination. A phantom apparition of his father lunges at him, causing Austin to fall over the second-story stair railing to his death.

The next morning, the real Sheriff Sheldon and his deputies arrive at the morgue to find Tommy and Austin dead, with the radio playing cheerfully on the counter. The sheriff notes that no storm occurred overnight, revealing that the entire blizzard was a supernatural illusion cast by the entity.

Jane Doe lies on the examination table completely unblemished, her incisions and surgical cuts miraculously healed and erased. Unable to determine what happened, the sheriff orders Jane Doe transferred to a medical facility in Richmond, Virginia. In the final shot, as the ambulance drives down the highway, Jane Doe's right big toe twitches and the attached bell gives a single, chilling ring, signaling that her trail of vengeance is about to claim a new set of victims.