Work on a building site is suspended when a skull is found. Dr Matthew Roney believes that this find is very important - a missing link in human development. Under pressure to allow building work to continue, Roney enlists the help of Professor Quatermass. Quatermass is in London fighting a loosing battle to retain control of his British Rocket Group. A metal object is discovered, believed to be an unexploded bomb. There's only one problem, the object is underneath the fragile skulls which are believed to be 5 million years old.

Uncovered, they discover that the interior of the object is empty, and a symbol consisting of five intersecting circles, which Roney identifies as the occult pentagram, is found etched on an interior wall which appears to hide an inner chamber.

The shell of the object is so hard that even a borazon drill makes no impression, and when the attempt is made, strange vibrations cause severe distress in the people around the object. Quatermass interviews the local residents and discovers that sightings of ghosts and other poltergeist activity have been common in the area for decades. Meanwhile, a soldier is carried out of the object in hysterics — he claims to have seen a dwarf-like apparition walk through the wall of the artefact, a description which matches a 1927 newspaper account of a ghost sighting.

Following the drilling attempt, a hole has somehow opened up in the wall which allows Quatermass and the others access to the interior chamber. There they find the remains of insect-like aliens resembling giant three-legged locusts, with stubby antennae on their heads giving the impression of horns. As Quatermass and Roney examine the remains, they theorise that the aliens might have come from a nearby planet which was habitable five million years ago — Mars.

Quatermass plans to use an invention of Roney's, an "optic-encephalogram", to see these visions. The device will record impressions from the optical centres of the brain, in effect showing whatever the subject is seeing, hallucinatory or not. He wears the device and goes into the craft, but it is Roney's assistant, Barbara Judd, who is affected most. Placing the device on her, they record what she "sees"—a violent, bloody purge of the Martian hive, to root out unwanted mutations.

Despite his warnings, the media event occurs, and the power cables that string into the craft fully activate it for the first time. Glowing and humming like a living thing, it starts drawing upon this energy source and awakening the ancient racial programming. Those people of London in whom the alien admixture remains strong fall under the ship's influence; they merge into a group mind and begin a telekinetic mass murder of those without the alien genes, an 'ethnic cleansing' of those that the alien race mind considers impure and weak.