Reality show contestant Kimberly Caldwell is driving through the West Virginia backcountry when she accidentally hits a teenager. She stops to help him, but he bites her lips off, revealing himself as one of the cannibals. She flees but runs into Three Finger, who splits her in half with his axe. Pa joins him in dragging her body halves away.
The Apocalypse: Ultimate Survivalist, a survival reality game show hosted by former U.S. Marine Colonel Dale Murphy, is in production at the West Virginia forest. Because of Kimberly's absence, the show's producer Mara reluctantly takes her place.
Other contestants include: Amber (lesbian Iraq war veteran), Elena (lingerie model), Jake Washington (former football player), Jonesy (skateboarder), and Nina Papas (graphic artist).
As the game starts, Three Finger and Pa murder the television crew and abduct Dale Murphy. Mara finishes a task and enters a cabin to find a telephone, and Nina follows her. While looking around the cabin, they hear the occupants return and hide in a bedroom. Mara and Nina witness a female cannibal, Ma, giving birth to a deformed baby. They are spotted by Ma's daughter, Sister, and escape through the toilet pit. They run into the woods, but Pa throws a hatchet which hits Mara in the head. Nina searches for the others as the cannibals collect Mara's corpse. At the lake, cinematographer M and Elena have sex before the former leaves, and Elena stays to tan in her underwear. When she hears a noise, she starts to get dressed as Sister emerges and slashes her to death with a machete while Pa and Ma hijack the RV and capture M.
Dale escapes captivity and battles Three Finger, ending the fight by shooting the cannibal into the lake with a shotgun. He then enters the mutant family's cabin. He finds the Old Man, the gas station attendant, who reveals how the cannibals' mutations were caused by inbreeding and consumption of effluent dumped in the river from an abandoned paper mill 30 years ago. The man, who is revealed to be the grandfather of Three Finger and the two other inbred mountain men who have been killed, attacks Dale to avenge their deaths. After a brief skirmish, Dale kills the old man by blowing him up with a stick of dynamite. Meanwhile, when Nina returns to explain her story, the three other contestants are eating some meat found by Amber and Jonesy. They then realize that they have been eating Kimberly's leg. They attempt to escape, but Nina gets separated from the group while they fight Brother and Sister. Jake rescues Nina from a pit, and they jump into the river to escape Sister.
After Amber and Jonesy are killed while looking for help, Nina and Jake enter the mill and find a garage with vehicles stolen from prior victims. They find the RV, and Jake enters it only to witness Ma decapitating M on a live feed monitor inside. Nina and Jake attempt to leave, but the cannibals capture them.
The next day, Dale sneaks into the compound to distract the cannibal family who were eating dinner. He kills Brother and Sister with a dynamite stick attached to an arrow. He frees Nina and Jake but is killed by Ma and Pa, who are incensed by the deaths of their children. Nina successfully escapes, but Jake wanders into a room fitted with a large meat grinder, where he is attacked by Ma and Pa. Nina returns to the mill and kills Ma and Pa with the meat grinder. Nina and Jake find Kimberly's sportscar and drive away.
Three Finger, who survives being shot by Dale, nurses the mutant baby, feeding it with a bottle of effluent and a human finger.
