Boos rang out from a pro-Pacquiao Las Vegas crowd as Mayweather's emphatic victory was confirmed by all three scorecards after 12 rounds of cat and mouse action.
Mayweather comfortably picked off his Filipino rival to snuff out any chance of the full-blooded slugfest that the more aggressive Pacquiao was hoping to ignite in front of the crowd of 16,507.
The win extended Mayweather's remarkable 19-year unbeaten record to 48-0, putting him within one fight of equalling Rocky Marciano's legendary milestone of 49-0.
Mayweather retained his World Boxing Council and World Boxing Association welterweight titles and seized Pacquiao's World Boxing Organisation belt by winning the fight on all three of the judges' scorecards.
"I am the American dream," said Mayweather. "I knew I had him from round one. I have so much experience I could calculate his moves. I was born a winner and I am going to die a winner.
Mayweather said he hopes the win will silence critics who accused him of ducking Pacquiao and hand-picking opponents he knew he could beat in order to keep his unblemished record intact. "Everyone said this guy could beat Floyd. That Floyd is a chicken."
Saturday's fight is widely believed to be the most lucrative in boxing history with revenues of $400 million.
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.
But when the results were announced the pro-Pacquiao crowd booed lustily and tried to drown out Mayweather's interview inside the ring.
Their Filipino star Pacquiao suffered the sixth loss of his career to go with 57 victories and two draws.
Pacquiao claimed he was hindered by an injured right shoulder that he hurt in training several weeks ago. "I did my best but my best wasn't good enough," he said. "From the third round on, I felt a pain in my shoulder."
Fans in the Philippines echoed the disappointment of those in the ring, crying foul over the judges' decision and claiming their man was robbed of a deserving victory.
They filled gymnasiums, cinemas and bars as the Southeast Asian nation of 100 million people stopped in its tracks for Pacquiao's battle with Mayweather.
There is no denying that the 36-year-old Pacquiao made Mayweather work for the victory and hit the American with "three or four" thundering shots.
He was the aggressor, pressing the action from the first round and was able to land some right-left combinations on Mayweather's head, especially on the ropes and in the final seconds of the early rounds.
But ultimately Pacquiao wasn't able to keep up his frenzied early pace for all 12 rounds and Mayweather, who was the bigger of the two fighters, managed to set traps which allowed him to slip in counterpunches and hard right hands that kept the Filipino southpaw at bay.
Even so, Pacquiao said he thought he did enough to earn the victory. "I thought I won the fight," he said. "He didn't do anything."
Mayweather reiterated his plans to retire after his next fight in September. "My last fight is in September," said Mayweather, estimated to have earned more than $200 million for one night's work. Pacquiao on the other hand will receive well over $100 million in a 60-40 purse split the fighters agreed to beforehand.
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