Pacquiao thrashed Margarito in a unanimous decision in the main event of an 11-bout card at Cowboys Stadium Saturday, with wide scorecard margins of 120-108, 119-109 and 118-110.
The 31-year-old displayed deadly accuracy, landing 411 of 713 power punches in taking his seventh organizational weight-class title.
Pacquiao, this time fighting for the 154-pound championship belt, also won crowns at 112, 122, 130, 135 and 140 pounds, and is the reigning WBO champion at 147.
He weighed in at 144 1/2 pounds and was 148 in the ring while Margarito weighed in at 150 pounds and entered the ring at 165.
ESPN.com reported the Mexican fighter suffered a fractured orbital bone in the lopsided loss.