As Prof. Bernard Quatermass (Brian Donlevy) struggles to gain government support for his Moon colonisation project, his interest becomes focused on reports of hundreds of meteorites landing in Winnerden Flats. Travelling there with Marsh, his colleague (Bryan Forbes), Quatermass finds a huge complex under construction, based on his lunar colony plans. Marsh discovers that an undamaged meteorite is shaped like a small stone rocket. It then cracks open, releasing a gas, leaving him with an odd V-shaped mark on his face. Black-clad guards from the complex arrive, armed with machine guns and sporting similar V-shaped marks, and take Marsh away, knocking down Quatermass and ordering him away.
An outer-space terrorist from a planet named Arous - a brain-shaped creature named Gor - arrives on Earth and possesses young scientist Steve March. Gor then proceeds to use his vast, destructive powers to bend the world to his will, threatening to wipe out the capital city of any nation that defies him.
A huge, blinking flying saucer that's approaching the Earth emits a glowing object. This object races ahead of it to intercept a man who's driving down a lonely road. It takes over the man's body and directs him to Central Labs, a U.S. research facility that's been tracking the saucer (supposing it to be an asteroid).
A flying saucer lands in the woods. A teenage couple, Johnny Carter (Terrell) and Joan Haydon (Castillo), while driving to their local lover's lane without the headlights on, accidentally run down one of the saucer's large-headed occupants.
Psychiatrist Dr. Hill is called to the emergency room of a hospital, where a screaming man is being held in custody. Dr. Hill agrees to listen to his story. The man identifies himself as doctor, and he recounts, in flashback, the events leading up to his arrest and arrival at the hospital:
Dr. Tom Anderson (Lee Van Cleef), an embittered scientist, has made contact with Zontar, a Venusian creature, while using his radio transmitter. The alien's secret motivation is to take complete control of the Earth by enslaving humanity using mind control devices; the alien claims it only wants to bring peace to our troubled world by eliminating all emotions. Anderson agrees to help the creature and even intends to allow it to assimilate his wife (Beverly Garland) and friend Dr. Nelson (Peter Graves).
Scientist Dr. Russell Marvin (Hugh Marlowe) and his new bride Carol (Joan Taylor) are driving to work when a flying saucer appears overhead. Without proof of the encounter, other than a tape recording of the ship's sound, Dr. Marvin is hesitant to notify his superiors. He is in charge of Project Skyhook, an American space program that has already launched 10 research satellites into orbit. General Hanley (Morris Ankrum), Carol's father, informs Marvin that many of the satellites have since fallen back to Earth. Marvin admits that he has lost contact with all of them and privately suspects alien involvement. The Marvins then witness the 11th falling from the sky shortly after launch.
Unaccountable, deadly malfunctions begin occurring at a top-secret government facility under the New Mexico desert where a space station is being constructed. Agents from the Office of Scientific Investigation (OSI) in Washington, D.C. are called in to investigate.
After a botched attempt at suicide, Nora King (Kathleen Crowley) revives and discovers that her building has no electricity or water. She soon realizes that Chicago is deserted when she wanders out into the empty, quiet streets. Stumbling over the body of a dead woman, she encounters Frank Brooks (Richard Denning), another person who has just recently revived after being beaten in a robbery.
In early 1950s southern California, Dr. Clayton Forrester (Gene Barry), a scientist who had worked on the Manhattan Project, is fishing with colleagues when a large object crashes near the town of Linda Rosa. At the impact site, he meets Sylvia Van Buren (Ann Robinson) and her uncle, Pastor Matthew Collins (Lewis Martin). Van Buren was told that the meteorite came down at a low angle, while Forrester observes it appears far lighter than normal for its massive size. His Geiger counter also detects it is slightly radioactive, but the object is still too hot to examine closely. Unable to account for these anomalies, Forrester is intrigued and decides to wait in town overnight for the object to cool down.
Late one night, young David MacLean (Jimmy Hunt) is awakened by a loud thunderstorm. From his bedroom window, he sees a large flying saucer descend and disappear into the sandpit area behind his home. After rushing to tell his parents, his scientist father (Leif Erickson) goes to investigate David's claim. When his father returns much later in the morning, David notices an unusual red puncture along the hairline on the back of his father's neck; his father is now behaving in a cold and hostile manner. David soon begins to realize something is very wrong: one-by-one he notices certain townsfolk are acting in exactly the same way. Through his telescope, David sees child neighbor Kathy Wilson walking in the sandpit, when she suddenly disappears underground. David flees to the police station for help, and he is eventually placed under the protection of health-department physician Dr. Pat Blake (Helena Carter), who slowly begins to believe his crazy story.