American Mayweather, 38, delivered a defensive masterclass against his Philippine rival, making the necessary adjustments after only a few rounds before disappearing out of sight.
Mayweather, who added the WBO welterweight title to the WBC and WBA titles he already owned, was awarded the fight 118-110, 116-112 and 116-112 by the three judges.
With his victory, Mayweather also cemented his status as the greatest pound-for-pound boxer of his generation.
The five-weight world champion is now undefeated in 48 professional fights, stretching back 19 years.
Six-weight world champion Pacquiao, 36, falls to 57 wins, six losses and two draws.
Tickets for the bout – billed as ‘The Fight of the Century’ – changed hands for as much as $350,000 (£232,000) and American fans were charged almost $100 (£66) to watch on television.
