A pickup truck parks unnoticed outside Evelyn and Darren Mountjoy’s house, while the couple plays Scrabble inside. When the Mountjoy’s dog barks at the front door, Evelyn lets it out to run into the woods. They hear the dog’s yelping outside, and the lights mysteriously go out. Darren orders his wife to hide in the basement while he loads his revolver. From the stairs, he sees the intruder approaching, and he fires. However, Darren soon realizes that the person he shot is his wife. Her hands and mouth are bound with duct tape. Suddenly, strange sounds rise behind him. They are voices, whispering backwards. Darren turns to see two men with demonic-looking faces coming towards him.
The next morning, Agents Reyes and Doggett look over the crime scene at the Mountjoy home in Weston, West Virginia. The couple’s bodies are sitting upright at the kitchen table, and Evelyn has a gun posed in her hand. The Scrabble board is laid out in front of them, blank, except for “DAEMONICUS” spelled out in the center. The word means “Satan” or “demon possession.” Doggett tries to fend the case off as merely some kind of Satanic ritual, but Reyes has other ideas beyond those based in reality. Her theories are confounded when three blood-slicked snakes squirm out of the bullet holes in Evelyn’s chest.
Although Scully is on leave and serving as an instructor at Quantico, the agents ask her to perform the autopsies. Evidence proves that Darren was most likely tricked into shooting his wife, and that he was held down and shot in a chair. The snakes were sewn into the body post-mortem. The facts show that the murders were man-made, but Reyes still believes that she felt the presence of evil in the house. With a lead about an escapee from a nearby mental institution, Reyes and Doggett question Dr. Monique Sampson about her patient, Kenneth Richman. Richman was a doctor who brutally murdered his own patients, but he had no prior knowledge of Satanic ritual. Dr. Sampson tips them off to a possible accomplice -- Paul Gerlach, a hospital guard who has recently gone missing.
Reyes and Doggett question Josef Kobold, a former professor who is now an inmate in the cell next to Richman’s. Kobold’s cryptic answers lead the agents to believe that he knows more than he is letting on. Meanwhile, the two demonic-appearing men from the Mountjoy attacks get out of their pickup truck in the woods. One shoots the other with a gun, then wipes the blood from his hands. The backwards whispers echo once more, but seem to be coming instead from Kobold. Dr. Sampson summons the agents back to the institution when Kobold asks for Doggett. The professor was also repeating the phrase, “Prince of the Apostles.” Kobold tells them that “He” is speaking and has killed again. He leads the agents to the woods, where Paul Gerlach’s body is found hanging upside down from a tree. He is wearing the demon mask and is staged in a mock-crucifixion pose, presumably put into such post-mortem. The “Prince of the Apostles” phrase refers to St. Peter, who was crucified upside down. This is known as the symbol marking the power of the anti-Christ.
Although Doggett believes Kobold is a master manipulator toying with them, Reyes is convinced that Kobold can somehow help them find the real perpetrator -- Richman. They turn to Kobold again, and he requests a larger cell with windows. Doggett is frustrated that Reyes wants to give in to the psychopath’s every whim, but Kobold is moved to another room, and Officer Custer is assigned to guard him. Kobold confronts Doggett with personal intimations about his own life that no one else would know. Doggett is uncomfortable, but before he can leave the cell room, Kobold’s eyes roll back and a strange sound emanates from his mouth -- voices, whispering backwards. Doggett calls for Reyes, who translates the word as “medicus,” or physician. The agents rush to the home of Dr. Sampson, who unbeknownst to anyone, has been followed home by the looming pickup truck. However, they are too late to save her, finding her body with a dozen hypodermic needles jammed into her face.
Scully reports that the needles contained the same medication that Dr. Sampson had treated Richman with, and he is determined to still be a suspect. Doggett furiously looks over at Kobold, held in restraints, knowing that he is really the one responsible for the crimes. Kobold watches as Scully tries to calm Doggett. The backwards whispers swell once more. Back at the mental institution, Doggett attempts to interrogate Kobold about his past knowledge of Satanism. Kobold lobs back insinuations that Doggett is competing with the long-lost Agent Mulder for Scully’s affection. Angrily, Doggett grabs hold of Kobold, but a thick orange goo violently spews from Kobold’s mouth. It keeps gushing uncontrollably as Doggett calls for a medic.
After an examination, Scully concludes that Kobold is completely normal. Reyes suspects that the orange bile is spiritual ectoplasm, but Doggett won’t be swayed by any more unexplainable theories. He is convinced that Kobold is a liar who is playing games with them. As Officer Custer guards Kobold’s room, a lightning storm competes with the ever-present whispers. Custer is drawn to the source of those whispers, and looks in Kobold’s room. Kobold’s face suddenly changes into the demonic mask.
Doggett calls Scully in her car. Kobold has identified something called “Happy Landing” as the place to find Richman. Scully recognizes it as an old marina she passes on her commute to Quantico, and she heads there alone. At the marina, Scully is attacked by a demon mask-wearing man. When Doggett and Reyes arrive with a pack of troopers, Scully is nowhere to be found. Kobold is held in shackles in a police car, and Doggett threatens him to tell where she is being hidden. All the professor can say is “Game’s over, Mr. Doggett. You’ve lost.” A gunshot rings out over the marina, and the agents find Scully unharmed, in an abandoned warehouse. Richman, having held her at gunpoint until Doggett arrived, shot himself. Reyes can’t figure out why he would do that, but Doggett quickly understands, and he runs after Kobold, who is escaping from the police car. Doggett shoots at the fleeing prisoner, and Kobold, hit, falls into the water.
Back at Quantico, Reyes and Doggett tell Scully that their case is not completely solved. It is understood that Kobold designed the crimes so that they would be on the case, and then researched all of their backgrounds on the internet. However, Kobold’s body has not been found, even though they saw him get shot. The body in the water is actually Officer Custer, the guard assigned to his cell. Kobold had selected his victims so that parts of their names spelled out the word “Dæmonicus.” He wanted the agents to see how brilliantly he could beat them at his game. By the time they realized it, Kobold would be too far away to get caught. Reyes is still unsettled. She did feel the presence of evil and believes that Doggett had the same premonition as well.