After losing radio contact for some considerable time with its control centre at the British Experimental Rocket Group, the rocket ship Q1 crash-lands in a field outside a Berkshire village. Professor Bernard Quatermass, head of the Group and designer of the craft, arrives on the scene, along with associate Dr Gordon Briscoe, to supervise the operation of saving the three-man crew.

The local fire brigade hoses down the white-hot rocket ship, and Quatermass orders the door to be opened by remote control, whereupon one of the crew members staggers out and collapses. The other two crew members, however, cannot be found, even though their still-sealed space suits are present in the ship. A search of the interior, reveals a jelly-like substance.

Despite warnings from Inspector Lomax of Scotland Yard, who is treating the situation as a potential murder case, Quatermass takes the surviving astronaut, Victor Carroon, to his research laboratory where Dr Briscoe can attempt to treat him. But Carroon does not respond to any stimuli, merely lying in a vegetative state, with any attempts at speech distorted.

He is subsequently moved to a nursing home, but his condition continues to deteriorate; his body begins to demonstrate signs of extreme physical change, with alterations to his bone structure and a degeneration of his skin. Carroon also becomes hypnotically attracted to a cactus in his room, and, although clearly fighting against the urge, is compelled to thrust his hand into the plant.

Analysis by Quatermass and Briscoe of the jelly-like substance found on the rocket ship indicates that it is broken down human tissue. Film taken during the mission by an automatic on-board camera indicates that something had entered the rocket ship when in space, apparently absorbing the other two crew members while leaving Carroon unconscious.

Carroon's wife, June, blames Quatermass for what has happened to her husband and is convinced that he bears no genuine concern for her husband's welfare, only for finding out what actually occurred during the space mission.

June hires a private detective to smuggle her husband out of the nursing home. But, accompanying him in a car following the abduction, and unaware that her husband had killed the detective during the escape, she catches a glimpse of his lower arm, which he had been trying to conceal. The arm has obviously been mutating and now resembles the cactus plant. She screams in horror and Carroon runs away.

From the evidence they have gathered, Quatermass and Briscoe now believe that Victor Carroon no longer exists, his body having been taken over by some kind of alien life form that invaded the rocket ship.

Now on the run, Carroon begins to manifest signs that the cactus growth is spreading over his entire body . Any life form with which he comes into contact is drained of its tissue and blood, including some animals in London Zoo; a sufficient vestige of his personality survives, however, for him to spare a young child who he encounters.

But his bodily change is rapidly accelerating, and what was Carroon is eventually transformed into a large tentacled monster. This creature makes its way to Westminster Abbey, where it is spotted during a live television broadcast, wrapping itself around some scaffolding in the vaulted roof. The Abbey is evacuated.

Quatermass has determined that the creature will soon be at a stage where it will emit spores, which, like the original creature, will feed off any living tissue. Briscoe calculates that within two hours the creature's reproduction cycle will be complete and that these spores will burst from its body to spread across London. If not stopped, the mushrooming life cycle of these creatures will eventually result in the human race being wiped out.

Quatermass destroys the creature by diverting all of London's power supply into the scaffolding on which it rests. With the creature dead, the professor departs the scene, emboldened in his determination to commence work on the construction of a new rocket, the Q2.