A meteorite crashes near Arborville, California. An elderly transient discovers, within the sphere, a massive slime mold-like substance (the Blob) that attaches itself to his hand. Three high school students, Brian, Meg and Paul, take him to a hospital. After Brian leaves, Paul witnesses the lower half of the transient melting from exposure to the Blob. As he calls for help, the Blob drops on top of him. Meg arrives to see Paul being devoured by the growing Blob. While she tries to free him, his arm dissolves off, Meg is thrown against a wall and knocked unconscious, and the Blob oozes out of the hospital as Paul attempts to scream in pain while dissolving inside the Blob one last time.
After Brian and Meg have unsatisfactory encounters with the police, they meet at a diner where Meg tells Brian about the Blob. Brian is incredibly skeptical of Meg's story. Brian's disbelief is shattered when the diner's handyman, George, is pulled head first through the sink drain by the Blob. It pursues them to the diner's walk-in freezer, but the Blob suddenly retreats after entering the freezer. After consuming the diner's owner, Fran Hewitt, who was trapped in a phone booth, the Blob reenters the sewers. Jacob Meeker witnesses the Blob enter the sewer and he investigates the dark and abandoned diner. Meeker discovers frozen fragments of the Blob near the open freezer door. Meg and Brian return to the police station, where the dispatcher tells them Deputy Briggs is near the meteor-landing site. They discover a military operation led by a scientist, Dr. Meddows, who orders the town quarantined. Brian escapes a military van and collects his motorbike. Meg is taken to town where she learns her younger brother, Kevin, is missing. Meg learns he and his friend, Eddie, have sneaked into the local movie theater. The Blob enters the theater and attacks the staff and then the audience. Meg arrives as the audience is fleeing the theater, rescuing Eddie and Kevin.
Brian eavesdrops on Meddows and learns that the Blob is a biological warfare experiment created during the Cold War that was launched into space because it was so dangerous. Learning that the Blob has entered the sewers, Meddows decide to trap it there, even if that means allowing Meg, Kevin, and Eddie to die. Brian is discovered listening in and evades military personnel by driving his motorcycle into the sewers. In the sewers, Meg and Kevin flee from the Blob when it emerges and devours Eddie. Kevin escapes to the surface by scaling a pipe and squeezing through a grate. A three-man team of soldiers find Meg with the Blob and they unsuccessfully attempt to kill it. Meg is saved by Brian and they ride away on his motorcycle through a tunnel until they crash. They run into the only surviving soldier of the three-man team who is in shock from watching the other soldiers die. Meg, Brian, and the soldier escape the sewer after Meddows unsuccessfully attempts to trap them with the Blob. Brian confronts Meddows in front of the townsfolk and Deputy Briggs. After failing to convince everyone Brian is contaminated and must die, Meddows attempts to shoot Brian, but is killed by the Blob as it oozes into his chemical suit and drags him into the sewer. Col. Hargis, second in command after Meddows, attempts to destroy the Blob by shooting it and dropping a bomb into the sewer, which only succeeds in angering it. Enraged, The Blob burst out of the ground and kills Hargis, and feasts upon the population and soldiers, impervious to the military's attempts to stop it. The town's Reverend Meeker proclaims the scene to be the prophesied end of the world, after which a failed flamethrower attack on the Blob sets him ablaze. Meg saves him with a fire extinguisher, and in the process blasts the Blob with it. The monster backs off. Remembering that it left them alone in the walk-in freezer, she realizes that it cannot tolerate cold.
The survivors retreat to the town hall and hold the Blob off with furniture-barricades and fire extinguishers, but it is a losing battle; the Blob engulfs half the building and devours Deputy Briggs. Brian goes to the town's garage and gets a snow maker truck that has canisters of liquid nitrogen attached. As the Blob is about to consume Meg and her family, Brian shoots snow at the creature, which is angered and knocks the truck over. As the Blob surges toward Brian, Meg lures it away from him toward the canisters, which she has rigged with an explosive charge taken from a dying soldier. She tries to get clear, but snags her foot between two pieces of metal, leaving her trapped. Brian regains consciousness and runs over to free her. The Blob is about to overrun them when the charge goes off, blowing up the canisters and covering the Blob with liquid nitrogen. The creature is flash-frozen, shattering into a mass of crystallized pieces. Moss Woodley has its remains stored in the town ice house.
Months later, at a tent-meeting church service in a field, Meeker, disfigured by his burn injuries, preaches a doomsday sermon resembling the Blob's attack. He is then shown to have a still-living piece of the Blob, trapped inside of a glass jar.
Who does the Blob devour?
Deputy Briggs