The first scene sets up the danger of the "Sumatran Rat-Monkey," a hybrid creature that "according to legend" resulted from the rape of tree monkeys on Skull Island by plague-carrying rats. Stewart, an explorer returning from the depths of the island with his guide and team, is carrying a rat-monkey in a cage and is stopped by fierce warrior natives that demand the return of the monkey. Stewart escapes with the cage to the rest of his team and a waiting Jeep, leaving his guide behind and the natives in hot pursuit. As the jeep takes off, Stewart's guide catches up and jumps on board. In the ensuing melee, Stewart gets bitten by the Rat-Monkey. Seeing the mark of the monkey's bite on his right hand, Stewart's men immediately hold down the infected explorer and amputate the appendage. A bite mark is then seen on his left arm, which swiftly results in the removal of that limb. Finally, they see a set of bloody scratches on Stewart's forehead and kill him. The title screen follows the man's dying scream, and as the opening credits roll the captured rat-monkey is shipped to Wellington Zoo in New Zealand.
Wellington, 1957, Lionel Cosgrove lives with his domineering mother, Vera. To his mother's dismay, Lionel falls in love with a local shopkeeper's daughter, Paquita, and while snooping on the two during a visit to the zoo, Vera is bitten by the Sumatran Rat-Monkey; she subsequently crushes its head. The animal's bite slowly turns her into a ravenous zombie. Lionel is horrified, but, ever the dedicated son, is determined to care for her. Despite his efforts to keep her placated with periodic doses of veterinary anesthetic, Vera starts murdering other townspeople, turning them into zombies. He tries to keep them locked away in the basement, while simultaneously trying to maintain his relationship with the completely oblivious Paquita. Vera escapes, however, and is hit by a tram.
As the townspeople assume she is dead, Lionel tranquilizes the still-kicking zombie for her funeral. After she is buried, he returns to the graveyard to administer more anesthetic, but is accosted by a gang of hoodlums. Vera bursts from her grave, resulting in more deaths and zombies. As their numbers grow, Lionel manages to keep the zombies under relative control with repeated injections, and tries to keep them concealed in his home. However, Lionel's uncle Les, arrives to try to wrangle with Lionel over his mother's estate. Uncle Les discovers the "corpses" and blackmails his nephew into giving up his inheritance in return for his silence.
Lionel reluctantly administers poison to the zombies ("killing" them) and buries them, just as Uncle Les and a crowd of his friends arrive for a housewarming party. However, the "poison" turns out to be an animal stimulant, and since the zombies came from the bite of an animal (the Rat-Monkey), it only gives them even more energy. The zombies burst from the ground to attack and infect the party guests in a gory finale.
Some of the guests are running, and some are being eaten by the zombies. Lionel goes into a room where he saw Paquita fighting with Uncle Les, and informs them of the zombie outbreak, which horrifies them. Uncles Les manages to get out through the window, while Lionel pulls out a large hanger with clothes, which distracts the zombies and gives Paquita a chance to escape. He later kills the zombified Void by splitting his body in half, but his intestines come to life and try to kill him. He escapes into the attic where he finds a vault containing a corpse. He notices that it is his real father. He stumbles down from the attic upside down while a rope hangs on his feet. Paquita, Rita, and Mandy barricade themselves in a room. A man was being eaten on the window and they try to help him, but when they pull him inside, his body is half eaten. Mandy screams and a zombie knocks her down and crushes his hands on her mouth, killing her. Paquita hides in a cabinet where she finds Rita. They go to the kitchen and barricade themselves there, but the zombified Mandy is there with the baby. The baby bites Rita's neck, and the two see Uncle Les screaming for help. They save him by pulling him inside, but the room was damaged so the zombies were able to get in. As the girls run upstairs, Uncle Les is bullied by the baby zombie as he follows it. He goes into the basement, where he sees Lionel's mother, who has turned into a giant zombie. She pulls him up and separates his spinal cord and head from his body.
As Paquita and Rita are chased by the zombies, Lionel appears and holds a running lawn mower, bottom outwards, with which he kills most of the zombies, with a great load of limbs, blood, and body parts flying around. The group are now fighting with dozens of zombies, animated intestines and spinal cords, severed heads, and disembodied legs. As Paquita fights some of the zombies, she notices something is wrong with Rita, and as she talks to her, a baby's hands appears on her ears and splits her head in half; the baby killing Rita. Just as it attacks Paquita, Mandy's head (impaled on a bulb) ignites, and manages to ignite gas flowing from an open gas pipe, setting the house ablaze, killing the zombified Rita in the fire. Lionel manages to kill all of the zombies, until his mother, who (possibly because she was the one originally bitten) has become a hyper-oestroegenized gargantuan monster with a grossly distorted head and spine, and huge, balloon-like breasts, pursues Lionel and Paquita to the rooftop. Paquita almost falls and hangs onto the edge of the roof, while Lionel finally confronts his mother about the truth regarding his father's demise. It is revealed that she drowned Lionel's father and mistress after she found them in the bathtub together. Lionel declares that he is no longer afraid of her, and she opens her womb, engulfing Lionel, closing him inside her body, declaring that he is 'such a good boy' and that 'none will ever you love you as much as (the one who bore you)' as Paquita screams in horror. Lionel's mother then tries to kill Paquita by removing her hands from the pole she's holding, and in an over-the-top Freudian "rebirth", Lionel cuts his way out of his mother's grotesquely changed, gigantified body using the cross he got from Paquita's grandmother, falling out in a river of blood, and then being 'reborn' from a pile of gore (placenta) after his mother falls into the fiery house below. Lionel and Paquita escape the burning building, and walk away arm-in-arm covered in gore, as the local fire department arrives on the scene to put out the flames.