In Antartica, an American research crew is getting ready for the upcoming winter. While preparing, a helicopter from a Norwegian research base flies in pursuing a dog they are trying to shoot. The Americans try to reason with the Norwegian, but he is shooting his gun hysterically and no one can understand what he is saying, so Garry (Donald Moffat) shoots him in defense. The dog is taken in as a stray. Wondering why the Norwegians were trying to kill the dog, MacReady (Kurt Russell) and a couple other team members go to investigate the Norwegian base. Everyone is dead. It appears that the Norwegians had discovered a crashed UFO and a body not far from it that they had brought back to their base to study. Along with the human bodies, the American team finds at the Norwegian base the burned and frozen corpse of a twisted creature, not man but not beast, either. They bring it back to their own base for an autopsy, but that muddies up the mystery.
That night the new stray is locked in with the sled dogs. The other dogs react with fear to the new addition, growling and snarling. Then, the new dog transforms into a creature with tentacles and starts killing the other dogs. It is killed with a flamethrower, the only thing that seems to truly hurt it.
One by one, the members of the team become taken over by the Thing. George Bennings (Peter Maloney) is discovered to be a Thing, but his transformation is incomplete, and the others torch him before the Thing can finish it's assimilation.
Dr. Blair (Wilford Brimley), a biologist on the American team, studies cells from this Thing, and watches them attack and replicate other kinds of cells. Realizing that something like this could take over the world if it got out, he kills the surviving dogs and destroys the helicopter and the communications equipment (injuring Windows (Thomas Waites) in the process), trapping the crew without hope of rescue. The others, seeing him as a threat, lock him in a storage shed outside.
Vance Norris (Charles Hallahan) succombs as well. He appears to have a heart attack, and when Dr. Copper (Richard Dysart) tries to revive him using defibrulator paddles, Norris' chest opens up and bites off Copper's arms. The others again use a flamethrower to destroy the Norris/Thing, leaving only it's head, which sprouts spider-like legs and tries to crawl away before that is destroyed as well.
At this point, MacReady leads the others in a test to determine who is infected. He suggests that everyone give a blood sample, and then those blood samples be burned. The theory is that each part of a Thing will try to survive independently, and therefor the blood would transform to defend itself. Everyone is tied up while the test is performed. Palmer (David Clennon) is discovered to be a Thing. He transforms and kills Windows before being set on fire and crashing through the wall to die in the snow.
The survivors go to check on Blair, and discover the shed empty but for a craft Blair had been building under the shed. Finally, realizing how pervasive the infection is and that there is little chance for survival, it is proposed that they blow up the base so the Thing can't get to the rest of the world. Nauls (T.K. Carter) disappears and is never seen again. Garry is killed by Blair who turns into the Thing. It destroys MacReady's detonator so instead MacReady throws a stick of dynamite at it. Both the Thing and the building explode, but MacReady survives. He stumbles to a shack to find Childs there. Neither of them know whether the other is the Thing, and they both sit ready to kill the other at the first sign. They take swigs of a bottle of whiskey as the camera shows a wide shot of the camp in flames.