The 32-year-old southpaw, despite being hampered by cramp in his left leg, dominated all 12 rounds against his defence-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.
