It's October 30, 1977 and Jerry Goldsmith (CHRIS HARDWICK) and Bill Hudley (RAINN WILSON) are two young men traveling across the state with their girlfriends, Denise Willis (ERIN DANIELS) and Mary Knowles (JENNIFER JOSTYN). About ready to run out of gas, they pull off on an exit that leads them to Captain Spaulding's Museum of Monsters and Madmen. Bill is fascinated by the place and asks many questions of Spaulding (SID HAIG), a bizarre fellow who convinces the four to take his tour.
During that, they learn about a local legend, Dr. Satan, who performed primitive surgery on mentally handicapped patients in hopes of creating a super race of humans. He was caught and hung, but his body mysteriously disappeared. After Spaulding informs them that the spot of the hanging is nearby, Bill convinces the others they must see it.
Along the way, they pick up hitchhiker Baby (SHERI MOON) who claims she lives nearby and knows of that macabre spot for which they're searching. When a local man, Rufus (ROBERT MUKES), shoots out their tire, however, they end up heading back to Baby's place where they await for their car to be repaired.
There, they meet Baby's bizarre "family," including Mother Firefly (KAREN BLACK) and Grampa Hugo (DENNIS FIMPLE), the disfigured and thus masked Tiny (MATTHEW MCGRORY), as well as the aggressive and long-haired Otis (BILL MOSELEY). Little does the foursome realize that these people have recently kidnapped five high school cheerleaders and are currently torturing them in sadistic ways.
When Denise's father, Don Willis (HARRISON YOUNG), informs the local police that she and her friends never arrived, he joins officers George Wydell (TOM TOWLES) and Steve Naish (WALTON GOGGINS) in a search for them. As they do so, the foursome quickly realize they're in deep trouble as the family sets its sights on them. From that point on, they try to do whatever they can to survive the gruesome and sadistic behavior that awaits them.