In the breathtaking wilderness of the Venezuelan tepui, British entomologist James Atherton makes a startling discovery by capturing two unique specimens of a prehistoric spider. These bizarre, primal arachnids lack sex organs, suggesting they function as laborers or soldiers in a hive-like society, which is particularly unusual among spiders. Tragically, one of these lethal spiders later bites Jerry Manley, a bedridden American nature photographer, leading to his untimely death due to a severe seizure caused by the venom.
Upon his demise, Manley's withered body is transported back to his hometown, Canaima, California, where it arrives at the local mortuary. Unbeknownst to the mortician, Irv Kendall, one of the highly dangerous spiders has clandestinely made its way into the coffin, ultimately escaping and infecting a crow that would later drop dead near the barn of Ross Jennings, the town's new family physician.
Having moved from San Francisco to take over the practice of the retiring doctor, Ross, alongside his son, harbors a common phobia of spiders. Their previously tranquil life is thrown into chaos when the lethargic offspring of the spiders begin to reproduce wildly, unleashing a swarm of infertile, drone-like descendants that threaten to obliterate their nest.
As the spiders commence their assault, members of the community begin to fall prey to their deadly bites. The alarming series of events is initiated by the sudden death of Margaret Hollins, which raises eyebrows about the hasty heart attack diagnosis given by Dr. Sam Metcalf. Shortly afterward, high school football player Todd Miller succumbs to the affliction following a routine examination with Ross, who earns the ominous title of "Dr. Death." The situation escalates when Metcalf himself becomes a victim and dies right in front of his wife, sending shockwaves through the town.
Perceiving the escalating peril, Ross seeks counsel from Dr. Atherton. The skeptical entomologist sends his dedicated assistant, Chris Collins, to assist Ross in his investigation. Their efforts lead them to exhume the bodies of Margaret and Todd, where they discover clear evidence of spider bites.
Further investigation into Metcalf’s residence yields two specimens of these lethal spiders, one of which has unfortunately died from natural causes. As they delve deeper, Chris reveals Atherton's finding of a new spider species, awakening a realization in Ross that these rampaging arachnids may be linked to the primitive species that Atherton previously uncovered.
As Atherton joins Ross, Chris, Milt, Sheriff Lloyd Parsons, and exterminator Delbert McClintock in Canaima, they confront a chilling reality: the spiders’ time is fleeting due to their careless reproduction. Atherton sheds light on the situation, explaining that the spiders they face are simply soldiers, dispatched at the whim of their commanding officer, referred to as "the general." To ensure the survival of their species, this general aims to produce a queen that breeds to fortify their ranks, a plan designed to usher in an era of evolution and dominate the world.
In their pursuit of answers, Ross, Chris, and Delbert stumble upon a horrifying revelation—one of the nests has taken hold in Ross's very own barn. In a frantic attempt to eliminate the impending threat, Delbert discovers that Atherton has met his fate, succumbing to a bite from the male spider while trying to capture the general. Undeterred, Chris swiftly evacuates the Jennings family from their nightmare, but Ross suffers a dark turn of events when he plummets through the floor into his cellar—home to the second nest, ruled by the queen and the general.
Seizing the moment, Ross displays courage by electrocuting the queen, but faces a daunting challenge in confronting the evil general. With his arachnophobia set aside, Ross fixes his attention on the critical task of incinerating the egg sac while Delbert finds himself trapped under debris, perilously close to becoming the general's next victim. Demonstrating quick thinking, Ross hurls the spider into the flames, but the general, though grievously burned, manages a leap from the flames as the egg sac hatches.
In a last-ditch effort, Ross grabs his nail gun, launching the burning spider back towards the nest with remarkable precision, effectively obliterating this imminent threat. Delbert rushes to rescue Ross from the debris, and together they finally conclude their battle, ensuring the extinction of the general, queen, and their nests, vanquishing the spidery menace.
As the Jennings family decides to depart from Canaima, an unexpected earthquake rattles San Francisco, prompting them to reflect on their newfound appreciation for the safety they have achieved.
