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, during the winter 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 dog 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 jabbering frantically in their native language. One of them pulls the pin on a grenade but clumsily throws it behind him. As the pilot frantically tries to find it in the snow, it explodes, killing him and taking the helicopter with it. The other man continues 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 and their doctor, Copper (Richard Dysart) go to investigate the Norwegian base. The whole base has been gutted by fire and explosions as there are holes in several of the walls in the interior of the complex. There is also a fire ax 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 examination. An autopsy performed by biologist Blair reveals nothing more than a normal set of internal organs despite a deformed, distorted exterior.
That night, the new stray husky is locked in a kennel with the team's 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 incident is discovered by dog handler Clark (Richard Masur), who watches horrified. Mac hears the sounds of the thing's unworldly groan and the cries of the other dogs; and he immediately responds by sounding the fire alarm, waking up the entire camp who converge on the kennel where they see the hideous dog-like creature seemingly consuming the other sled dogs. Part of the creature separates from the rest and pulls itself up through the ceiling. After shooting at the beast with their guns, the 'thing' is burned with a flamethrower.
An autopsy done by Blair 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 its image to appear in the animal or person it kills. The team also watches a videotape of the Norwegian team working at a remote location, forming a circle around an object in the ice and using Thermite charges to uncover it.
The following day, MacReady flies with Palmer and Norris to the site where the Norwegians were working. They find an alien spaceship in the open crater and rappel 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 above the crash site, they find a block of the ice cap missing where the thing was discovered and removed by the Norwegians. Back at Outpost 31, Mac theorizes that the Norwegians awakened the creature after thawing its ice block and it immediately began to attack them.
That evening, Blair studies cells from the 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, just over 3 years) after first contact.
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 Blair's (Wilford Brimley) notes and found that Blair believes the organism's cells are still alive and active in the burned remains of both creatures. Blair has also theorized that the alien might have imitated a thousand other lifeforms across space.
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 escaped through the storage room window. 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 incinerate him alive and then burn the remains of the two other creatures along with him.
Realizing that something like this could take over the world if it got out, Blair seemingly loses his mind, killing the surviving sled dogs and destroying 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, subdue him, 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. Doc Copper suggests that he develop a blood serum test to see who might be infected. Copper finds that the blood bags in the lab have been slashed open, making their contents useless. Copper believes that someone deliberately destroyed the blood to prevent the test from happening. Gary and Copper become suspects because of their access to the blood storage while Clark is regarded with suspicion because of his proximity to the imitation dog. All three 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 and the outside temperature drops severely, they are forced to hunker down, all of them continuing to be paranoid and distrustful of one another. Mac talks to Fuchs, who only has a few weak theories from Blair's notes. Fuchs recommends that everyone prepares their own meals and eat only out of cans.
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 charred 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 ragged and dirty clothing with Mac's name on it in the oil furnace inside 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 a 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 detaches, 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 an attempt on MacReady's life with a scalpel; he is shot and killed by McCready. 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 another 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. The Palmer-Thing's entire head splits open and turns into a giant mouth, biting 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, which MacReady then blows up with a stick of dynamite. MacReady is then forced to torch Windows with the other flame thrower, since he is now infected and the Thing is assimilating his body.
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; Blair had escaped through the floor and was secretly building a small spacecraft in the tunnels under the camp. They are confused when they see Child's running off into the storm, but at that moment, the compound's power suddenly turns off. It is then they realize that Blair is the last Thing creature and that it wants to freeze into hibernation until the rescue team finds it since it has no way out. Finally, realizing how pervasive the infection is and that there is little chance for survival, it is proposed that they blow up the base to prevent the Thing from freezing again. MacReady, Nauls and Garry begin setting fire to the complex with Molotov cocktails.
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. MacReady comes face-to-face with the huge, tentacle Blair/Thing, which destroys his detonator. In a last-ditch effort, MacReady throws a lighted stick of dynamite at it. Both the Thing and the rest of the compound explode, but MacReady survives. He stumbles to his ruined shack to find Childs there, who claims he had seen Blair and had gotten lost in the storm running after him. Neither of them know whether the other is the Thing, and they both sit ready opposite and facing each other, 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, along with a wiry laugh from MacReady, 'The Thing' comes to a close.