A fierce thunderstorm lashes Bridgton, Maine, bringing chaos as a tree collapses on the lakeside home of artist David Drayton, his wife Stephanie, and their eight-year-old son Billy. The following morning, as they assess the damage, an ominous mist rolls over the lake. Determined to gather supplies, David and Billy set off with their neighbor Brent Norton.
Upon entering the supermarket, they witness police cars racing down the street, prompting panic when a frightened local named Dan Miller rushes in, warning the shoppers of an unseen menace lurking within the mist. As a civil alert siren blares ominously, store managers Ollie Weeks and Bud Brown take charge, sealing off the supermarket just as the mist envelopes the building. In a desperate attempt to return home to her children, a woman bravely ventures outside.
Despite David's protests, bagger Norm recklessly attempts to fix the store’s emergency generator, only to be seized by a grotesque tentacled creature, leaving everyone in shock. Amidst the mounting tension, David and Ollie lead the customers to fortify the storefront windows. Meanwhile, Mrs. Carmody, a fanatical preacher, starts to expound on her apocalyptic beliefs, claiming that the mist heralds the end times. Skeptical of the situation, Brent assembles a small group, defying David's warnings, to seek help outside, but they are swiftly attacked and presumably meet a grim fate.
Inside the store, David fosters alliances with several patrons, notably Amanda Dunfrey and Irene Reppler, teachers who clash with Carmody over her fervent rhetoric. Armed with a revolver from Amanda, Ollie, a former regional shooting champion, prepares for the growing threats. Night falls, and as enormous flying insects swarm toward the lights, terrifying pterodactyl-like creatures crash through the windows, unleashing havoc. The ensuing chaos results in multiple casualties as people scramble to escape. Notably, Carmody remains untouched by the chaos, further emboldening her as she gathers followers through her dire interpretations of their plight.
In a courageous but ill-fated venture, a small group led by David sets out to a nearby pharmacy seeking medical supplies, only to be met by deadly giant spiders that kill two members, reinforcing Carmody's influence as she offers divine protection. The following day, revelations emerge that local military personnel had inadvertently opened a portal to the creatures' realm due to a top-secret government project. Indignant, Carmody's supporters sacrifice a soldier, Jessup, banishing him from their ranks. Outside, he faces imminent doom, devoured by a colossal praying mantis-like being.
While preparing to leave the supermarket the next morning, Carmody intercepts David's group, declaring that Billy has been chosen as the next sacrifice to placate the creatures. In a moment of desperation, Ollie shoots and kills Carmody, leading the traumatized survivors to make their escape. However, as they navigate the parking lot, Ollie falls victim to the voracious praying-mantis creature, while others are also claimed by the spider-like monsters. Meanwhile, Bud dashes back to the store, seeking refuge with the other patrons.
As David, Billy, Dan, Amanda, and Irene reach David's car, they attempt to flee. Upon driving through the foreboding mist, David is heartbroken to discover his home in ruins and Stephanie lying dead. Overwhelmed by despair, he flees the town, encountering a massive six-legged beast before eventually running out of gas. Faced with hopelessness, the adults opt for a tragic end; David takes the gut-wrenching decision to shoot Billy and the remaining survivors with his last four bullets, before resigning himself to the creatures outside.
In a shocking turn, the mist suddenly dissipates, revealing a team of U.S. Army soldiers, who are engaged in eradicating the creatures and restoring order. It dawns on David that his son and the others he has sacrificed were on the brink of rescue. He drops to his knees in anguished disbelief, crying out in despair for the irreversible tragedy that has unfolded.
