The crew of an American research base in Antarctica is surprised by a member of a nearby Norwegian team arriving in a helicopter, shooting at a husky. The panicking man manages to accidentally blow up the helicopter after landing, and then shoots meterologist George Bennings in the leg while continuing to try to kill the husky. With the team unable to communicate and find out what’s going on, he's simply killed by Captain Garry while the husky is taken into the base. Dr. Copper suggests they head to the Norwegian base for answers, and their pilot R.J. MacReady reluctantly takes off into the oncoming snow. While they're gone, the husky approaches an unseen person.
At the Norwegian base, MacReady and Copper find the entire team is dead and their corpses mutilated, plus a large hollow ice block and a strange deformed corpse that's been burned. They bring it back to their own base, and biologist Blair finds that despite outward appearances, it has a completely normal set of human organs. In the meantime, radio man Windows has been unable to contact anyone for weeks, and dog handler Clark is sent to put the husky in the kennel with their own dogs. Once left alone, it mutates into a grotesque monster that sprays fluid onto the other dogs, and everyone's attempts to kill it are unsuccessful until chief mechanic Childs takes it out with a flamethrower.
Blair does an autopsy and discovers the alien Thing was in the process of assimilating the other dogs until they interrupted it, and the team also finds the spot where the Norwegians dug it out of the ice, where it apparently crashed millennia ago and had been frozen until now. After further research, Blair determines even some cells in the burned bodies are still alive, just as one of them infects Bennings and quickly becomes a near-perfect copy except for his hands. After disposing of it, Blair goes to extreme measures to stop the Thing from spreading across the world, killing the dogs and destroying their radio and vehicles. The others lock him in a shed fearing for his sanity, but he gives a warning that Clark is the most likely to also be infected after spending so much time with the husky.
Copper suggests they test samples of everyone's blood against the base's clean emergency supply to see if any of it reacts, only for them to find the blood supply has all been destroyed by someone who didn't need to break the lock, adding Garry and Copper to the prime suspect list. As a storm moves in, the two of them plus Clark are drugged and tied up while the others keep up the search. Blair's assistant Fuchs discovers a torn jacket belonging to MacReady, and shortly afterwards the others find him burned to death, apparently a suicide before he could be infected. MacReady then teams up with the cook Nauls, who also finds the jacket and gets away to warn the others.
MacReady breaks back into the base and threatens to blow everyone up with dynamite if they attack him, insisting the Thing used the jacket to set him up. The tense standoff causes geologist Vance Norris to have a heart attack, and Copper is brought in to resuscitate him. But Norris turns out to be infected as Copper's attempt to zap his heart caves his chest in, which then turns into a mouth that bites off Copper's arms. One part of the Thing with a twisted version of Norris' face climbs onto the ceiling while his actual head grows spider-like legs and tries to crawl away, but MacReady takes the flamethrower to them both. Copper is also killed in the confusion.
The battle gives MacReady the idea that any part of the Thing that splits off has its own consciousness that will fight to survive, so they decide to test how everyone's blood will react to a heated wire. Before the test can start, Clark snaps and tries to attack MacReady with a scalpel, and is shot dead. Almost everyone, including Clark, passes the test, but then the blood from assistant mechanic Palmer springs onto the floor, and he transforms now that his cover is blown. His head splits into a giant jaw that kills Windows before the flamethrower will start again and take him down, and they also burn Windows' body before he can turn as well.
Childs is left to guard the base while the others go out to test Blair, only to find he's been infected, and built a spaceship out of helicopter parts. They realize the Thing's goal is now to go back into hibernation until the rescue team arrives, and resign themselves to sacrificing any chance of their own survival to kill it. They blow up most of the base, but then Blair arrives and painfully shoves his hand into Garry's face to kill him, while Nauls wanders off to an uncertain fate. MacReady has a final faceoff with Blair after a full transformation, including mutated dogs erupting from him, before blowing the monster up with his dynamite and completing the base's destruction.
As MacReady slumps down exhausted, Childs arrives and claims he went looking for Blair too. The two of them simply sit and face each other down, unclear if either has been infected, and with no hope of rescue either way.
