A group of stranded motorists is lost in the woods of West Virginia, where they're hunted by three cannibalistic mountain men.
Reality show contestant Kimberly Caldwell is driving through the West Virginia back country searching for the location of her next project. While driving, she accidentally hits a human figure. She stops to help him, but he bites her lips off, revealing him to be Brother, a mutant cannibal. She attempts to escape but runs into Three Finger, who splits her in half vertically with an ax. He and Brother drag her body away as her intestines lie on the road.
Alex Miles and her friends Trey, Sophie and Brent go into the woods of West Virginia on a rafting trip. As they are camping, Sophie and Brent begin to have sex, and Alex leaves to find Trey. Three Fingers arrives and kills Sophie with an arrow. The arrow also wounds Brent, who flees. As Three Finger begins to eat Sophie, Alex watches in horror from behind a bush. Meanwhile, Trey returns and tries to flee, but is chased down and killed by Three Finger. Brent is killed by a wire trap, leaving Alex the sole survivor. Later, Sheriff Carver and Deputy Lane receive a report about the missing group.
After The Hillicker Brothers (Three Finger, Saw Tooth and One Eye) Wrong Turn 4: Bloody Beginnings, now along with the help of serial killer Maynard Odets start a murderous rampage near the city of Fairlake, Greenbrier County, West Virginia, where they first murder news reporter Kaleen Webber.
Daria and Nick ride their bikes deep in the Hobb Springs Bike Trail. After bathing in a small watering hole, they start having sex. Meanwhile Three Finger is spying on them. Afterward, they ride their bikes again until Nick falls off and discovers that an unknown assailant has shot him with a bow and arrow. The assailant, Three Finger, then kills Nick with an arrow through the face. Daria attempts to flee only to ride into a strip of barbed-wire planted by One Eye and Saw Tooth. Three Finger then decapitates and kills her with a machete.