Trish Jenner and her brother Darry are traveling home from college for spring break. As they drive through the Florida countryside, an old, rusty truck tries to run them off the road. The vehicle eventually passes them, and they later see the same truck parked next to an abandoned church with a man sliding what appears to be a body wrapped in bloodstained sheets into a large pipe sticking out of the ground. The man notices Trish and Darry watching him and attempts to run them off the road a second time.
After escaping, Darry convinces Trish to go back to the church and investigate. At the church, Darry hears noises coming from within the pipe and crawls inside with Trish holding on to his feet, but he ends up falling in after being startled by a swarm of rats. At the bottom, he finds a dying man with stitches running down his stomach, and hundreds of other bodies sewn to the walls and ceiling. After Darry escapes, the two flee the scene and attempt to contact the police at a diner. At the diner, they are phoned by a strange woman who warns them that they are in danger. Confused and frightened, they ignore her warning. Trish and Darry leave, with two police officers providing a security escort. As they travel, the police learn that the church has caught fire, and any evidence of bodies has been destroyed. The police are then attacked and killed by the mysterious trucker, who loads their bodies into his truck.
Fleeing, Trish and Darry stop at a reclusive old woman's house, and beg her to call the police. The woman complies until she notices the driver hiding in her yard. She attempts to kill him, but the driver kills her and reveals his inhuman face to Trish and Darry, before pursuing them once again. Trish runs the driver over with her car, but they are horrified to see a giant wing tear through his trench coat and flap frantically in the air. They drive to the local police station, where they are approached by psychic Jezelle Gay Hartman. She reveals herself as the woman who called them at the diner and tells them the true nature of their pursuer: it is an ancient creature, known as "The Creeper", which hunts every twenty-third spring for twenty-three days to feast on human body parts, which then form parts of its own body. She also tells them that it seeks out its victims through fear, and, by smelling the fear from Trish and Darry, it has found something it likes, but she does not know what.
The wounded Creeper arrives and attacks the police station. After cutting off the power, it gains entrance to the cells and feasts on prisoners to heal. The Creeper is swarmed by police but kills a number of them and evades capture. Trapped, Jezelle warns Trish and Darry that one of them will die a horrible death. Darry demands to know who, and Jezelle looks at Trish. The Creeper finds them, spares Jezelle as she does not have anything it wants, and pursues Trish and Darry. The Creeper corners them in an upstairs interrogation room. After sniffing and tasting them, the Creeper throws Trish aside and chooses Darry. Trish offers her life for her brother's, but the Creeper escapes out of the window and flies away with Darry.
The next day, Trish is picked up by her parents, and Jezelle returns home in regret. The final scene shows the Creeper in its new hideout, an abandoned factory, where it is revealed that he has removed the back of Darry's head and taken his eyes.
