Ben Mears, an aspiring writer, returns to his childhood hometown of Jerusalem's Lot, hoping to find inspiration for his new book. He quickly rekindles his romantic feelings for local resident Susan Norton, immersing himself in the comforting familiarity of the place. However, the tranquility is shattered when a mysterious European named R.T. Straker opens an antique shop in town. Straker's arrival coincides with unsettling events as he takes residence in the notorious, long-abandoned Marsten House.
Stranger still, a large coffin is soon delivered to the basement of his new home, leading to the chilling disappearance of Ralph Glick, a middle school student. It becomes apparent that Ralph has been kidnapped, sacrificed to Straker's master, a terrifying vampire named Kurt Barlow. Despite a frantic search by townsfolk, Ralph's fate remains a mystery, and newcomer Ben finds himself unfairly blamed for the bizarre occurrences that ensue.
Barlow, a force of terror, preys upon Ralph's brother, Danny Glick, who meets a tragic end only to resurrect as a vampire, inflicting his curse on gravedigger Mike Ryerson. Concerned for Mike's well-being, Matt Burke, a school teacher, discovers his ill state at a bar and brings him to the local physician, Dr. Cody. Observing troubling symptoms, Matt senses something sinister. Events take a drastic turn when they witness Danny soaring into Matt's home, prompting him to warn Ben, Susan, Cody, and Sheriff Parkins Gillespie.
As they investigate Mike's lifeless body, they realize he has succumbed to vampirism. A desperate group forms to confront the horrors unfolding in their town, encountering Danny in the process. When Danny attempts to manipulate his friend Mark Petrie into letting him in, Mark bravely stands his ground, resisting the sinister temptation. The following day assures another crushing blow as Cody learns of Danny's mother's tragic death, furthering the despair engulfing Jerusalem's Lot.
Cody boldly confronts Matt about the vampire menace, and he reveals essential knowledge on how to defeat them. In a moment of bravery, Mark and Matt initiate a dangerous mission to invade the Marsten House, hoping to eliminate Barlow. However, Straker cunningly captures them, sealing their fate in the basement, resulting in Matt's horrific fate of becoming one of Barlow's minions. With chaos reigning, Straker also snatches Mark, forcing Ben, Susan, and Cody to investigate a fresh lead regarding Danny's mother at the morgue. In a dreadful twist, they discover her powers have been corrupted, and while trying to protect themselves, Cody narrowly avoids transformation using a rabies shot.
As Barlow's minions unleash terror on Jerusalem's Lot, turning a significant number of residents into vampires, the desperate struggle intensifies. The following day offers fleeting hope as Mark manages to escape and confronts Straker, ending his dark influence. Seeking guidance, Ben, Susan, and Cody turn to Father Callahan for insight on Barlow. Mark relays critical information about the vampire lord's whereabouts, and as they venture towards the Marsten House, they fall victim to Matt, now undead.
In a sweeping tide of horror, the vampires overrun the town as chaos ensues. Sheriff Gillespie, instinctively trying to flee, faces a brutal end at the hands of the very monsters they seek to combat. In a heart-wrenching betrayal, Susan learns that her mother has allied with Barlow, leading to her own bite in a bitter twist of fate. [Father Callahan] attempts to warn Mark's parents, but the ruthless Barlow arrives, delivering an unmerciful end to them.
Desperate and fearful, Mark seeks shelter in his treehouse while Ben takes Susan to the protection of the church. Unfortunately, Cody struggles to cure her, and as Susan fully succumbs to her transformation, she escapes into the night, leaving behind an emotionally shattered Ben.
Eager for vengeance, Mark seeks out Barlow, discovering fresh horrors in Straker's shop, where he finally confronts Danny. Together, Ben and Cody connect the dots, suspecting the local drive-in theater holds vital clues about the vampires' activities. In a gripping scene where they prepare to confront the now-vampiric Susan, tragedy strikes as Cody finds herself shot by Susan's mother.
As dusk settles, the vampires converge, launching a deadly assault on Ben, while Mark manages to finish off Susan's mother, inadvertently exposing the remaining vampires to sunlight, resulting in their destruction. Amidst the chaos, Barlow emerges as a final obstacle for Mark, but Ben steps forward to protect him, ultimately delivering the fatal blow to Barlow with a staking maneuver. In the wake of devastation, Ben and Mark drive away from their beleaguered hometown, carrying with them the burden of loss and resilience as they leave the wreckage of Jerusalem's Lot behind.
