In a high tech underground facility, senior technicians Gary Sitterson (Richard Jenkins) and Steve Hadley (Bradley Whitford) discuss plans for a mysterious ritual. A similar operation undertaken by their counterparts in Stockholm has just ended in failure.
American college students Dana Polk (Kristen Connolly), Holden McCrea (Jesse Williams), Marty Mikalski (Fran Kranz), Jules Louden (Anna Hutchison), and Curt Vaughan (Chris Hemsworth) are spending their weekend at a seemingly deserted cabin in the forest, a cabin recently acquired by Vaughan's cousin. From their underground facility, where they possess significant technological control over the area in which the cabin is situated, Sitterson and Hadley manipulate the teenagers by intoxicating them with mind-altering drugs that hinder rational thinking and increase libido. They take bets from the different facility departments on what kind of monster will attack the teenagers and discuss the failures of similar rituals in other nations.
In the cabin's cellar, the group finds many bizarre objects, including the diary of Patience Buckner, a cabin resident abused by her sadistic family. Dana recites incantations from the journal, inadvertently summoning the zombified Buckner family despite Mikalski's warnings. By releasing pheromones, Hadley successfully induces Curt and Jules to have sex. Attacked by the marauding Buckner zombies, Jules is decapitated while Curt escapes to alert the group. Marty, a frequent marijuana smoker, discovers concealed surveillance equipment before being dragged off by one of the Buckners and apparently killed. Later, the Facility workers learn that the ritual in Japan has also ended in failure, ending Japan's streak of success, and confirming that the American ritual is humanity's last hope. It becomes apparent that the ritual involves blood sacrifice.
Curt, Holden, and Dana attempt to escape in their RV, but Sitterson triggers a tunnel collapse to hinder their flight. Curt jumps a ravine on his motorcycle in an attempt to flee and alert the authorities, only to crash into a camouflaged force shield, killing him. Holden and Dana retreat to the RV to plan their next move, but one of the Buckners, hiding within all along, stabs Holden as they are driving away, resulting in the RV crashing and sinking into a lake. Dana escapes and swims ashore and is beset in turn. As she is attacked, Sitterson, Hadley, and their staff celebrate her impending death and the successful completion of their ritual, viewing the events from their underground facility.
The celebration is interrupted by a phone call from "downstairs" pointing out that Mikalski has survived. His heavy marijuana use has apparently rendered him immune to Sitterson and Hadley's manipulations. He rescues Dana and shows her to a hidden elevator he discovered under a grave. They take the elevator into the underground facility, where a menagerie of monsters, utilized by Sitterson and Hadley, are imprisoned. Dana correlates them with the knickknacks in the cabin's basement and realizes that those items gave victims the opportunity to choose the circumstances that will lead to their deaths during the ritual. Cornered by the facility's security personnel, she and Marty release the multitude of monsters, including zombies, a werewolf, a giant snake, wraiths, a unicorn, and a merman, among others, who wreak havoc and slaughter the staff.
Fleeing further, Dana and Marty discover a temple where they are confronted by The Director. She explains that, every year, worldwide rituals are held to appease the Ancient Ones; malevolent beings living beneath the surface of the earth, one of them under their own Facility. The Ancient Ones are kept in perpetual slumber through their annual ritual, shown to be unique to the tropes of each region. The American slasher film ritual requires the killing of five young people embodying certain archetypes: the whore (Jules), the athlete (Curt), the scholar (Holden), the fool (Marty), and the virgin (Dana). The order in which intended victims perish is flexible, so long as the Whore dies first and the Virgin survives or dies last. The Director urges Dana to shoot Marty, completing the ritual and thus saving humanity. But the standoff is interrupted by a Werewolf that attacks Dana. The zombie Patience Buckner suddenly appears and kills the Director. Deciding that humanity is not worth saving, Dana and Marty share a joint as an Ancient One stirs, its giant hand emerging from beneath the temple floor, destroying the cabin and the Facility and killing them.
How many are required to be killed in order to maintain the slumber of The Ancient Ones?
Five