Picking up immediately where the first film ended, Marybeth is attacked by Victor Crowley, but manages to escape. Jack Cracker finds her, pulls her out of the river, and takes her back to his cabin. After finding out her last name, he forces her to leave, telling her that if she wants help, she needs to see Reverend Zombie. Moments after she leaves, Jack views Shapiro's camcorder, which he found in the swamp. The footage shows Shapiro filming different topless women, including Misty and Jenna. It also further reveals Shapiro's plan to venture into the swamp. After Jack finishes watching the video, he is killed by Victor Crowley, who gouges his intestines out and strangles him with them until he decapitates him.
Marybeth returns to Reverend Zombie's shop and, after demanding to speak with him, he reluctantly lets her in. It's revealed that Rev. Zombie had a small business going on with Shawn, the tour guide who was murdered the night before, and the boat was one of his own. After learning her last name, he tells her that her father was one of the boys responsible for causing the fire that led to Victor Crowley's death. He also tells her that Thomas, Victor's father, cheated on his wife Shyann with her nurse Lena after she was diagnosed with stomach cancer. Moments before dying, Shyann placed a curse on the child conceived by Lena from the affair. Months later, Lena died after giving birth to the deformed Victor Crowley. After Thomas accidentally killed Victor whilst trying to save him, he confronted the three boys responsible for the fire, but due to his violent attitude, and the shotgun he threatened them with, they, along with their parents, denied it. Thomas became a shut-in and eventually died ten years later of a broken heart. The story is then complemented by various scenes in which the undead Victor slaughters anyone who wanders into Honey Island Swamp.
Marybeth tells Reverend Zombie she wants to go back and retrieve the remains of her father and brother. He agrees, but tells her she must bring a family member with her. After she leaves, Zombie calls Justin, Shawn's brother, and reveals Shawn never returned with the boat. He lies, saying they are going into the swamp to find Shawn and the boat. He tells Justin to summon a group of hunters, specifically a man named Trent Graves to go with them. Marybeth returns home, where her uncle, Bob promptly shows up. He tells her she must stay away from Reverend Zombie, but reluctantly agrees to accompany her to a recruitment meeting in Zombie's shop. Zombie tells the hunters he will pay them $500 each to retrieve his boat and $5,000 for the head of Victor Crowley. He tells Trent he will pay him double to go, and Trent agrees. The hunters proceed to venture into the swamp with Marybeth and her uncle.
As night descends, they find the boat and, as the rest leave, two of the hunters, Cletus and Chad stay by the boat while the others fan out. Marybeth, Zombie, Justin, Bob and Trent look for Crowley's shed, as well as the bodies of his victims. Along the way, Zombie explains to Justin that Trent and Marybeth's father and uncle were the kids who started the fire that led to Victor's death. Zombie believes that if Crowley kills Bob and Trent, his soul will be at peace and he will finally leave the swamp. After not finding the bodies in the shed, they check the main cabin. Meanwhile, the rest of the hunting party are systematically murdered by Victor: Chad is violently hacked in the face with Victor's hatchet, and Cletus' face is mutilated by a boat propeller. While Layton and Avery are having makeup sex, Victor appears and decapitates Layton. Avery tries to run away, but Victor chops her between the legs and in the chest with his hatchet. Finally, John and Vernon are simultaneously split in half from the groin up with a long chainsaw. While searching the cabin, the remaining party members hear Victor outside.
As they hide, Justin tells Marybeth of Zombie's plot to get her uncle and Trent killed after Marybeth tells Justin that Shawn is dead. As she runs to warn Bob, Justin jams the door shut with a chair, but Victor appears behind him and kills him by wearing half his head away with a belt sander. Bob, in an attempt to save Justin, accidentally releases Victor. Marybeth attempts to attack him, but is tossed against the wall. Victor then on seeing Trent immediately goes after him and spearing him into the kitchen where the final battle occurs. Despite Victor's strength, Trent uses the nearby surroundings to his advantage, temporarily pinning Crowley against a support. He beats Victor with tables and chairs, but when Trent tries to kill Victor with a cleaver. Victor kills him by breaking his leg, then severs the top half of his head by kicking it against a table. Meanwhile, Zombie grabs Marybeth and drags her out of the house, trapping Bob inside with Victor. Zombie restrains Marybeth while she screams as she hears Bob being murdered by Victor inside. She falls to the ground in tears, and Zombie declares, "That's it. All over," and claims Victor Crowley is dead.
Marybeth tells Zombie that she will report his crimes to the police, but Zombie responds by preparing to shoot her. Only now does Marybeth reveal that Bob was not her real uncle; her father's brother had died of leukemia when she was twelve, and Bob was her father's best friend. Zombie turns to see Victor breaking through the wall of the cabin, now realizing his plan to kill Victor Crowley has failed. Zombie advances towards Victor and attempts to choke him, but Victor kills him by severing him in half before ripping out his severed spine, effectively skinning him alive. Just after Victor tosses Zombie's skinned upper body into the woods, Marybeth strikes him in the forehead with his own hatchet, knocking him to the ground. She then hysterically beats his head into a bloody pulp. She eventually stops and walks off, just as Victor's hand twitches. She then returns with Zombie's shotgun and fires the gun into the remains of his head, seemingly killing him.
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