During a Growth Opportunity graduation, (a parody of Erhard Seminars Training), a couple named Terry and Charlie are offered a ride from an old woman and are driven into the woods. After the old woman's car stalls, two inbred killers appear and attack; Charlie is decapitated with a machete in the backseat while Terry is brutally assaulted before being garroted by the old lady. It is revealed that the dual killers named Ike and Addley are the woman's sons.
Meanwhile, three women who have been friends since college—Trina, Abbey, and Jackie—prepare for an annual "mystery weekend" trip, where one of them arranges a getaway in a location unknown to the other two. Jackie, who lives in New York City, has planned a camping trip for them in the Deep Barons, a forested area in rural New Jersey. Trina, a glamorous model living in Los Angeles, and Abbey, who returned to Chicago after college to care for her ailing mother, travel to New Jersey, where Jackie picks them up. After stopping at a nearby store for supplies, they arrive at their destination and begin to camp. While in the woods, they begin to explore, sitting around the campfire telling stories and having fun by swimming and fishing. Unbeknownst to them, they are being stalked by Ike and Addley. In the middle of the night, Ike and Addley attack the women, binding and gagging them. The three are taken by Ike and Addley to a ramshackle home in the woods where they live with their unhinged mother, whom they impress by torturing people. The brothers tie the women to exercise equipment inside the home, but Jackie is swiftly selected by Mother to be the brothers' first victim and is taken outside. Addley rapes Jackie while Ike photographs it, and Mother looks on encouragingly.
Abbey and Trina awaken the following day and plan to escape while Mother and her boys exercise outside. During their exercise routine, Mother is alarmed when she spots her deformed sister Queenie—who lives in the woods and subsists on vermin—roaming in the distance. Inside the house, Abbey and Trina discover Terry and Charlie's bodies, and find a brutalized Jackie hidden inside a drawer. The three women manage to escape and flee into the woods. While Ike searches for the women, Addley remains at home with Mother where he questions Queenie's existence and if Mother's claims are just a ploy to keep the boys at home with her. As Jackie is unable to move quickly because of her injuries, Trina and Abbey become separated. Trina finds the car destroyed and is chased by Ike, while Jackie peacefully dies of her wounds. Ike eventually loses track of Trina, and she reunites with Abbey for revenge against Mother and the brothers.
The next morning, Abbey and Trina arm themselves with weapons and begin to invade the cabin to avenge Jackie. Trina castrates Addley with a clawhammer before Abbey suffocates him. When the women drag Addley's body outside, Ike leaps from a second-story window and attacks them. Enraged over his brother's death, Ike tries to strangle Trina before Abbey pours Drano down his throat. He chases the women into the house, where Abbey slams a television set on his head before Trina stabs him to death with an electric knife. With the brothers dead, the girls confront Mother in the basement where she is watching television, and sadistically suffocate her with a pair of inflatable breasts. With their vengeance complete, the two girls make a burial for Jackie and prepare to leave the woods before they are suddenly attacked by Queenie who leaps at them from behind the bushes.
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