In 1906 Shanghai, anthropologist Professor Sir Alexander Saxton (Christopher Lee) is returning home to England via the Trans-Siberian Railway to Moscow. He brings with him a large crate containing the prize from his expedition in the mountains of Manchuria: the frozen remains of a primitive humanoid creature, which Saxton is sure is the missing link in the evolutionary chain. Also on board is Dr. Wells (Peter Cushing), a colleague of Saxton's from the Geological Society of London.Mysterious deaths occur even before the train sets out. A known thief is found dead on the platform after having looked into the crate. His corpse is discovered bleeding from the eyes, which have turned blank and white. A slightly unbalanced, Rasputin-esque monk named Pujardov (Alberto de Mendoza) claims that the contents of the crate is evil. Pujardov is the spiritual adviser for Count Maryan Petrovski (Jorge Rigaud) and his wife, Irina (Silvia Tortosa), and he tries to demonstrate to them that the crate is an omen of evil: in a bizarre rationalization, he claims that where there is evil, there is no place for the sign of the cross, and a piece of chalk fails to make the marking of the cross on the side of the crate. Saxton dismisses it as a trick and discredits the monk.Saxton is eager to keep his find a secret from everyone, especially Dr. Wells, but Wells pays the baggage man (Víctor Israel) to look into the crate when everyone is gone and tell him what's inside. Later, the man does this and is also killed by the creature, which possesses a glowing red eye. After gazing at the red eye, the man's eyes begin to bleed and turn white until he falls down dead. The ape-man quickly picks the lock of the crate just like the Chinese thief did back at the beginning of the train's voyage. The creature leaves the crate and places the baggage man's corpse inside instead; the others discover it later and Saxton is forced to come clean about his discovery. Inspector Mirov (Julio Peña) represents authority on the train, and he tries to keep the news of the death quiet among the passengers, while simultaneously searching for the creature.A beautiful woman insinuates herself into Dr. Wells' compartment; she is Natasha (Helga Liné), and she uses her feminine charm to convince Wells that she is a lady in distress. In reality, Natasha is a spy intent on pilfering a block of steel belonging to the Count - who knows the formula for its creation - from the train's safe. She is recognized by Yevtushenko (Ángel del Pozo), a prominent engineer who knows he has seen her before. Wells dines with the both of them in the dining car, but Mirov summons him and his assistant, Miss Jones (Alice Reinheart) to perform an autopsy on the baggage man. When they remove the top of his skull, they find that his brain is strangely smooth; Wells concludes that the brain has somehow been "drained" of all knowledge and memory. Later, when he sees a boiled fish with a white eye, he decides that this is the reason the eyes of the victims turn white; the memories and information are absorbed through the eyes, causing this reaction.The fossil continues to haunt the train and kills two guards, eventually overcoming Natasha when she sneaks into the baggage compartment and attempts to remove the steel block from the safe. Wells happens upon the murder scene and the fossil tries to attack him, but it is gunned down by Inspector Mirov, who stares at the creature and then collapses into unconsciousness.In a strange experiment, Saxton, Wells and Jones discover images embedded in liquid inside the eye of the fossil, images that reveal a prehistoric Earth, as well as a view of the Earth from outer space. They deduce that the real threat is a formless alien creature that was simply inhabiting the body of the fossil, and that it has now transferred itself to someone else on board the train. These fears are confirmed when Jones is found dead in the baggage compartment, attacked by the Inspector and drained of her brain, her eyes white and bleeding. The monk senses the evil presence inside of the Inspector and pledges allegiance to it, declaring it to be Satan. Yevtushenko becomes a victim, too, when the creature learns that he has studied the laws of physics and theories of space travel.When news of the murders on the train is wired to Siberian authorities, the train is stopped and an intimidating Cossack named Captain Kazan (Telly Savalas) boards with a small group of his men. Mirov is discovered to be the creature and is shot and stabbed, but not before the alien presence transfers itself to the monk. The passengers all evacuate to the caboose, while the monk murders Kazan and his men by draining them of their brains.The creature attacks the Count to absorb his knowledge about steel; using the combined knowledge of the minds it has absorbed, the creature intends to build a vehicle that will allow it to escape Earth. When it threatens the Countess, Saxton arrives and confronts it with a shotgun and a powerful light, which renders its deadly red eyes temporarily ineffective. Playing for time, the creature tempts Saxton by revealing that it is a formless energy that came to Earth millions of years ago from another galaxy, and was accidentally left behind by its own kind; it has survived by transferring itself to each form of life that has evolved over time. As such, it possesses all of the knowledge that Saxton so desperately wants - including, it claims, the knowledge to cure disease and end hunger. Saxton, however, decides that the alien is too dangerous to be left alive. Realizing that Saxton cannot be bargained with, it resurrects all of its victims as white-eyed zombies. Saxton and the Countess fight through the zombies back to the caboose, where the others are waiting. As Saxton and Wells desperately work to detach the caboose from the rest of the train, Kazan's superiors in Moscow send a telegraph to the next station ahead, ordering them to divert the train to a siding overlooking a precarious cliff. The operators follow this order, speculating that a war has broken out. Just as Saxton and Wells uncouple themselves from the rest of the train, it crashes over the cliff and explodes into a fireball as it hits the ravine below. The caboose rolls to a safe stop precariously near the edge, where the survivors watch the fire consume the train and the unearthly inhabitants within it.