Millions of years ago, a spacecraft of an advanced humanoid alien race arrives on Earth. One of the aliens consumes a dark liquid, causing its body to disintegrate and fall into a nearby waterfall. We see its DNA break down and recombine, seeding Earth with the building blocks of life.
In the year 2089 on the Isle of Skye off the shore of Scotland, archaeologist couple Elizabeth Shaw (Noomi Rapace
) and her boyfriend Charlie Holloway (Logan Marshall-Green
) discover a star map in a cave which they record among the remnants of several otherwise unconnected ancient cultures. They interpret this as an invitation from humanity's forerunners. Peter Weyland (Guy Pearce
), the elderly founder and CEO of the Weyland Corporation, funds the creation of the scientific deep space research vessel called the USS Prometheus to follow the map to the distant moon of LV-223 several light years from Earth.
The ship's crew travels in hibernation stasis at light speed while the android David (Michael Fassbender
) stays awake at the pilot control to monitor their entire voyage. In 2093, the ship arrives in the orbit around LV-223 (Note: it is not the same planet first seen in the 1979 movie 'Alien' as confirmed by Ridley Scott in an interview with Simon Mayo and Mark Kermode on Friday June 1st on BBC radio 5 live. 'Alien' is set on LV-426). After being awakened from hibernation, the crew are informed of their mission to find the ancient aliens, called "Engineers" who may be the original humans. They also view a holographic message from Weyland himself, who tells them about his funding for the mission and that he has since died.
Mission director Meredith Vickers (Charlize Theron
) orders them to avoid any direct contact and to return if the aliens are found. The Prometheus lands near an alien structure (resembling a large temple-like pyramid) and a team including Shaw, Holloway, and David explores it, while Vickers and Captain Janek (Idris Elba
) remain aboard the ship and monitor their progress.
They find several cylinder-like artifacts, a monolithic statue of a humanoid head, and the decapitated corpse of a giant alien, thought to be one of the Engineers. Other bodies are later found in the structure, and the species is presumed to be extinct. They view archive footage of holographic Engineers running down the corridors reacting to a long-ago emergency (also of note: the alien Engineers are dressed in the exact same bio-mechanical spacesuits that the dead alien "Space Jockey" wears in the crashed spaceship in the original 'Alien' movie, thus confirming the connection between them as one and the same extraterrestrial species).
David secretly returns a cylinder to the ship, while the remaining vessels in the chamber begin leaking a dark fluid. A rapidly approaching storm forces the crew to return to Prometheus, leaving crew members Milburn (Rafe Spall
) and Fifield (Sean Harris
) stranded in the pyramid structure after becoming lost trying to find the way out. Shaw insists they take the Engineer's head back to the ship with them and they barely make it back alive.
In the ship, Shaw and medic Ford (Kate Dickie
) analyze the Engineer's head, and discover that its DNA is identical to that of the human race. But upon exposure to their breathable atmosphere, the severed Engineer's head decomposes rapidly and disintegrates into dust. Meanwhile, David investigates the cylinder and discovers a small ampoule containing a small amount of black fluid. He intentionally infects Holloway with the substance, hiding it in a drop of liquid on his finger and briefly tapping it into a glass of champagne Holloway drinks to celebrate their discovery. Later, Shaw and the infected Holloway have sex. Holloway later looks in a mirror and sees his eyes are changing.
Back inside the structure, Fifield and Milburn are attacked by snake-like creatures. Milburn is killed, and a corrosive fluid (yellow acidic blood) from one of the creatures melts Fifield's helmet, exposing him to the dark liquid leaking from the cylinders.
The next morning after the storm subsides, the Prometheus crew returns to the structure and finds Milburn's corpse. David discovers a room containing a living Engineer in stasis and a holographic star map highlighting Earth. Holloway's infection rapidly ravages his body, and he is rushed back to the ship. As he visibly deteriorates, Vickers refuses to let him aboard, and immolates him with a flame thrower at his own request.
A medical scan reveals that Shaw, despite being sterile, is pregnant. David subdues her to return her to Earth in stasis, but she escapes and uses an automated surgery pod in Vickers' quarters to extract a cephalopod-like creature from her abdomen. Weyland is found to have been in stasis aboard the ship, and it's revealed that Vickers is his daughter. Weyland explains to Shaw that he intends to ask the Engineers to help him avoid his impending death.
A mutated Fifield attacks the hangar bay and kills several crew members before being killed himself. Janek theorizes that the moon they are on was used by the Engineers as a military base until they lost control of their biological weapons, namely the cylinders and the black fluid they contain. The remaining crew return to the structure and awaken the Engineer, who is occupying what is discovered to be a space ship (the same design as the derelict alien space ship seen in 'Alien' and 'Aliens'). David speaks an alien language to the Engineer, who responds by decapitating him and killing Weyland and Ford. Shaw escapes from the alien ship as it is activated by the Engineer. The still-active David reveals it is going to release the ampoules on Earth. Vickers orders Janek to return to Earth, but Shaw convinces him to stop the Engineer's ship. Janek and his two surviving crewmen take off and crash the Prometheus into the Engineer's ship while Vickers flees in an escape pod. The disabled Engineer ship crashes onto the planet, falling onto Vickers, crushing her. The ship continues to tumble and nearly crushes Shaw, but she escapes.
Shaw goes to the escape pod to retrieve supplies and finds that her aborted but still alive alien offspring has grown to gigantic size. The Engineer survives the crash, enters the escape pod and attacks Shaw, who releases the tentacled creature. It subdues the Engineer by thrusting a tentacle down its throat. Shaw recovers David's remains from the alien ship, and together they activate another Engineer ship. Shaw and the remains of android David then take off to travel to the Engineers' homeworld in an attempt to understand why they created humanity and why they later attempted to destroy it.
In the final shot, in the Prometheus escape pod, an alien creature (very similar but not the same Alien as seen in the other movies) bursts out of the dying Engineer's chest.