Ridley Scott's 3D science fiction epic pulls in £2 million to lead the top ten, with Men in Black 3 and Snow White and the Huntsman unmoved from last week at numbers two and three respectively.
Broadway adaptation Rock of Ages makes a disappointing debut, entering the chart at number four.
Despite a star-packed cast including Tom Cruise, Catherine Zeta-Jones and Russell Brand, the musical earns just over £1 million from 479 locations.
Rounding out the top five is horror film The Pact.
Elsewhere, the chart sees new entries from Cillian Murphy's Red Lights at number six and a debut at eight for Noel Clarke's sports movie Fast Girls.
The UK box office top ten in full:
1. (1) Prometheus - £2,009,955
2. (2) Men in Black 3 - £1,544,429
3. (3) Snow White and the Huntsman - £1,297,559
4. (-) Rock of Ages - £1,003,107
5. (4) The Pact - £475,936
6. (-) Red Lights - £445,109
7. (5) Avengers Assemble - £376,991
8. (-) Fast Girls - £355,700
9. (8) What to Expect When You're Expecting - £248,185
10. (6) Top Cat: The Movie - £246,283
Watch the stars of Prometheus discuss the movie with Digital Spy below: