In the opening shot, an alien spaceship flies through space and enters Earth's atmosphere near Antarctica. Whether or not the ship crashes or lands on Earth is unknown.
In Antarctica, the winter months of 1982, a helicopter flies hurriedly after a husky. The man riding next to the pilot shoots a rifle and drops grenades hoping to kill the dog. The runs toward an American research base, Outpost 31, where a 12-man research crew is getting ready for the upcoming winter. The helicopter, which they see is from a Norwegian research base, flies in and lands. The Americans watch puzzled as two men that emerge from the helicopter speak frantically in their native language. One of them pulls the pin on a grenade but clumsily throws it behind him. As he frantically tries to find it in the snow, it explodes, killing him and taking the helicopter with it. The pilot (named Matias in the prequel) is shooting his rifle hysterically and talking frantically; no one can understand what he is saying and the man shoots Bennings (Peter Maloney) in his left leg. The camp leader Garry (Donald Moffat) shoots and kills the gibbering man in defense.
Puzzled about why the Norwegians were trying to kill the dog, MacReady (Kurt Russell) the team's helicopter pilot, their doctor, Copper (Richard Dysart) and Norris (Charles Hallahan), go to investigate the Norwegian base. The whole base has been gutted by apparent fires and explosions as there are holes in several of the walls in the interior of the complex. There is also a fire axe stuck into one of the walls. Everyone is dead; one of them had barricaded himself in the radio room and is still sitting frozen in his chair, his wrists and throat slit in an apparent suicide. Mac and Copper explore further, finding a large and empty block of ice. Outside in the snow, along with one or two burned human bodies, Mac and Copper find the burnt 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 husky is locked in with the sled dogs. The other dogs soon react with fear to the new addition, growling and snarling. The new dog suddenly transforms into a hideous creature with tentacles and crab's legs and starts attacking the other dogs. The scene is discovered by Clark (Richard Masur), who tends to the dogs and he watches, horrified. Mac hears the sounds of the thing's unworldly groan and he immediately responds by sounding the fire alarm, waking up the entire camp who converge on the dog kennel where they see the hideous dog-like creature seemingly consuming the other sled dogs. After shooting at it with their guns, the 'thing' is killed with a flamethrower. (Note: fire is apparently the only effective weapon against the alien creature which can hurt as well as kill it.) An autopsy on the thing's remains reveals its secret: the "thing" is an alien organism that imitates other life forms by attacking, and either digesting or dissolving them and reshaping it's image to appear in the animal or person it kills.
The following day, MacReady flies with Palmer and Norris to the crash site of where the Norwegians found the UFO after watching a videotape of the discovery of something buried under the ice, and the Norwegians using thermal charges to melt the ice on the spaceship. They find the alien spaceship in the open crater and haul themselves down to look around. Mac asks Norris how long the ship has been entombed; Norris estimates that it's been there for at least 100,000 years. Up near the crash site, they find a block of the ice cap missing where the thing was discovered and chopped out of the ice by the Norwegians. Back at Outpost 31, Mac theorizes that the Norwegians awakened the creature and it immediately began to attack them.
The team decides to place the creature's remains in a storage room. The assistant biologist Fuchs (Joel Polis) asks to speak privately with Mac; he tells Mac that he's been looking through the biologist Blair's (Wilford Brimley) notes and found that Blair believes the organism's cells are still alive and active. Blair has also theorized that the alien might have imitated a thousand other lifeforms across space.
That evening, Blair studies cells from this Thing, and watches them attack and replicate other kinds of cells on his computer. Typing his report into his computer, the computer replies that the possibility that one or more team members may be infected by the alien organism is 75%, and that if the alien reached civilization, the Earth's population will be infected and taken over by the alien organism exactly 27,000 hours (around 37 months) after first contact.
While Windows (Thomas G. Waites) and Bennings prepare the room to store the remains recovered from the Norwegian base, it begins to move under the blanket it's been covered with. Windows returns to the room to find Bennings being attacked, wrapped in tentacles. Windows gets the other team members but Bennings has vanished, running out the back door. They find him in the snow, his transformation by the alien nearly complete except for his hands, which are hideously large and grotesque shapes. Mac and the team incinerates him alive and buries his charred body in the snow.
Realizing that something like this could take over the world if it got out, Blair kills the surviving sled dogs and destroys the helicopter and the communications equipment (injuring Windows in the process), trapping the crew without hope of rescue. The others, seeing him as a threat, lock him in the camp's tool shed and sedate him.
The next morning, fear and paranoia circulates around the camp as nobody knows who may be the thing or who isn't. When blood plasma in the storage room is found to to be tampered with, which a scientific test that could have been used to find out who or who isn't human, Gary and two others (Dr. Copper and Clark) become suspects because of their access to the storage room. As a result they are quarantined by MacReady who takes over as the 'de facto' leader of the team to find out who may be the Thing. When a 'whiteout' storm (an Antarctic storm resembling a winter hurricane) hits the camp, they are forced to hunker down, all of them paranoid and distrustful of one another.
The following evening, Fuchs, trying to do research on how the Thing can reproduce and multiply, is waylaid when one of the unseen persons infected, disables the power to the lab. In going after it, Fuchs is killed (off-camera) and his body is found outside in the snow a few hours later by Mac, Nauls and Windows. Either the Thing burned Fuchs to death, or Fuchs burned himself in a suicide to prevent him from being taken over. Mac tells Windows to return to the main building while he goes with Nauls to his shack to investigate: when he left two days before, he'd turned out the lights and they're back on.
Some time later, Nauls returns to the camp, nearly collapsing because of the cold. He tells the others he'd found clothing with Mac's name on it in the oil drum near MacReady's shack. As they were struggling back to the main compound, Nauls cut Mac's safety line and made a break for it. Mac is locked outside and breaks the window in another storeroom to enter. He arms himself with a small bundle of dynamite and threatens to blow himself and the rest of them up if they don't back away. When Childs (Keith David) and the others rebel against MacReady (and to express their suspicion that he may be the Thing), Norris collapses when he appears to have a heart attack. When Dr. Copper tries to revive him using defibrillator paddles, Norris' chest suddenly opens up into a monstrous mouth and bites off Copper's arms. MacReady uses a flamethrower to destroy the Norris/Thing, leaving only it's head, which sprouts spider-like legs and tries to crawl away before it 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 poked with a hot piece of wire. The theory is that each part of a Thing will try to survive independently, and therefore the blood would transform to defend itself. Clark makes another attempt on MacReady's life, he is shot and killed by him. Everyone is tied up (including the dead Clark and Copper) while the test is performed. Windows is the first to be tested, and turns out to be human; MacReady arms him with a flamethrower to torch anyone who might be a Thing. As MacReady continues the test (testing the dead bodies of Clark and Copper whom are not infected), he openly accuses Garry of being a duplicate, but instead finds that Palmer (David Clennon) is a Thing clone. As Palmer transforms, MacReady's flamethrower misfires and Windows hesitates to kill the Palmer-Thing, which proves to be a fatal mistake as Palmer-Thing's entire head splits open and turns into a giant mouth, which is used to crush Windows' head. MacReady manages to get his flamethrower working and sets the Palmer-Thing on fire which crashes through the wall to die in the snow. MacReady is then forced to torch Windows with the other flame thrower, since he is now infected and the Thing is coming back through him.
MacReady and the three remaining survivors, Childs, Garry, and Nauls (T.K. Carter) are revealed to be not infected. While ordering Childs to stay behind to watch the camp, MacReady, Garry and Nauls go to check on Blair to give him the blood test, and discover the shed empty, save for a space craft Blair had been building under the shed. When the power in the whole compound turns off, the survivors discover that Blair is the last Thing creature and he must be stopped. 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. Childs runs off, and MacReady, Nauls and Garry set fire to the complex with dynamite to prevent the Thing from freezing itself again.
In venturing down into the basement of the camp to set TNT charges, Garry is killed by the infected Blair. Nauls disappears and is never seen again. Then, MacReady comes face-to-face with the huge, tentacle Blair/Thing, which destroys his detonator. So instead, MacReady throws a lighted stick of dynamite at it. Both the Thing and the building explode, but MacReady survives. He stumbles to a ruined 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. (MacReady is definitely not the Thing, but there is a strong possibility that Childs might have been taken over when he wandered off earlier). They take swigs of a bottle of whiskey as the camera shows a wide shot of the camp in flames. Both men, exhausted and wary of each other, sit among the burning wreckage.... waiting for the fires to go out and the winter weather to consume them. On that dark note, and with a wiry laugh from MacReady, 'The Thing' comes to a close.