Will Smith's science fiction blockbuster pulls in £2.9 million to secure the number one spot ahead of Sacha Baron Cohen's comedy The Dictator.
Men in Black III's opening haul is significantly down from its predecessors. Men in Black opened to £7.07 million in 1997, while its follow-up took £6.19 million in 2002.
Avengers Assemble lands at number three, while new release What to Expect When You're Expecting and Dark Shadows completes the top five.
Elsewhere, the top ten sees new entries from Wes Anderson's Cannes Film Festival opener Moonrise Kingdom at number seven and low-budget Finnish sci-fi movie Iron Sky at ten.
The UK box office top ten in full:
1. (-) Men in Black III - £2,953,736
2. (1) The Dictator - £1,078,155
3. (2) Avengers Assemble - £872,664
4. (-) What to Expect When You're Expecting - £661,617
5. (3) Dark Shadows - £409,560
6. (4) American Pie: Reunion - £362,323
7. (-) Moonrise Kingdom - £251,760
8. (5) The Raid - £116,340
9. (6) Beauty and the Beast 3D - £69.795
10. (-) Iron Sky - £66,076
Watch Josh Brolin discuss Men in Black III with Digital Spy below: