In a bout branded boxing's latest "Fight of the Century" Mayweather took his unblemished record to 48-0 adding the Filipino great's World Boxing Organization title to his World Boxing Association and World Boxing Council crowns.
Pacquiao fell to 57-6 with two drawn, never able to mount the kind of sustained aggressive attack he needed to earn the decision.
Soon after the fight, beaten Pacquiao revealed right shoulder injury.
Even so, he said he thought he did enough to earn the victory.
"I thought I won the fight," the boxer said. "He didn't do nothing."
In fact, Mayweather did what he does best, skilfully thwarting Pacquiao's offense.
Although his punches didn't come in the bunches that Pacquiao's did, there were plenty of telling blows.
Ringside judge Dave Moretti scored the bout 118-110 for Mayweather, while judges Glenn Feldman and Bert Clements both scored it 116-112 for the American.
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