By Mark Lamport-Stokes
The 32-year-old southpaw, despite being hampered by cramp in his left leg, dominated all 12 rounds against his defense-minded American opponent to improve his career record to 53-3-2 with 38 knockouts.
It was Pacquiao's 14th consecutive win since his loss to Erik Morales in Las Vegas in March 2005, and enhanced his status as the world's best pound-for-pound boxer.
Fighting for the second time since winning a seat in his country's national congress last year, Pacquiao gained one-sided verdicts from all three judges -- 119-108, 120-108 and 120-107.
"It wasn't my best performance but I did my best," Pacquiao said ringside in front of a sellout crowd of 16,412. "My leg tightened up in the middle rounds and I couldn't move.
"This is the same problem I had when I fought (Juan Manuel) Marquez so we are going to have to work on this."
Pacquiao sent Mosley crashing to the canvas in the third round with a searing straight left but, despite pressing for the rest of the fight, he was unable to stop an opponent seemingly more interested in survival.
"I got him with a lucky shot," Pacquiao said of the knockdown. "Mosley is not slow. He is fast. He was waiting for me to make a mistake and he wanted to counter. I was careful with that.
"I think he felt my power. But what am I going to do if my opponent doesn't want to fight toe-to-toe."
"Sugar" Shane Mosley, an 8-1 underdog against the 10-times world champion, slipped to 46-7-1 with 39 knockouts and was booed for much of the bout because of his defensive approach.
"Manny is an exceptional fighter with good speed and power, power that I didn't get hit with before," the 39-year-old American said. "It was a strong knockdown punch. I really felt it. I was pretty stunned, surprisingly stunned.
"It didn't seem like a big shot to me when he threw it but the impact was very strong. I fought my best but I came up a little short. We will go back to the drawing board."
Pacquiao's trainer Freddie Roach, who has long admired three-division world champion Mosley for his boxing intelligence, felt the American should now consider retiring from competition.
"I don't think he tried to win this fight," Roach told reporters. "I think he just tried to survive and when you get to that point in boxing, it's time to call it a day."
Loud chants of "Manny, Manny, Manny" rang out in the Garden Arena before the two fighters made their way to the ring.
Mosley came out first, led by American rapper and actor LL Cool J, before Pacquiao followed with Jimi Jamison of U.S. rock band Survivor singing the group's 1982 hit "Eye of the Tiger."
With the crowd again chanting "Manny, Manny, Manny" Pacquiao began to find a rhythm and he landed several telling combinations before ending the second round with a right hook followed by a straight left.
In round three, Mosley connected with another solid right before the Filipino sent the American crashing to the canvas with a crunching straight left set up by a right jab, only the third time Mosley had ever been knocked down.
The rest of the fight followed a similar pattern with Pacquiao, despite his cramped left leg, continually forcing Mosley to retreat as the American focused mainly on defense and survival.
In the 10th round, the Filipino was surprisingly adjudged to have been knocked down after being pushed to the canvas by Mosley. Fired up, Pacquiao ended that round in aggressive mode, hitting Mosley late on with a withering left.
With the crowd repeatedly chanting "Knock him out, knock him out", Pacquiao kept coming forward in the final two rounds but was unable to finish his opponent off.
(Editing by Patrick Johnston)