Pacquiao won every round on two ringside scorecards in extending the remarkable run that has made him the most exciting fighter in the sport.
He also won the ungrudging respect of a veteran fighter who has been in with some of the best in the world.
"I fought the best fighter in the world," Mosley said. "He has exceptional power, power that I've never been hit like this before."
Pacquiao knocked down Mosley with a left hook in the third round, a punch that sapped Mosley's willingness to engage. Pacquiao ran after Mosley the rest of the fight, but the former champion who has never been stopped in 18 years in the ring managed to stay away enough to finish the 12th round upright.
Pacquiao won 120-108 on one scorecard, 120-107 on a second and 119-108 on the third. The Associated Press had him winning 118-110.
For Mosley, the fight was strikingly similar to his bout a year ago against Floyd Mayweather Jr. -- except this time Mosley didn't even land a big punch like he did early on against Mayweather. Mosley's biggest moment on this night came when referee Kenny Bayless mistakenly ruled that Mosley knocked Pacquiao down in the 10th round when he didn't even hit him with a punch.
The knockdown that wasn't spurred Pacquiao on as he went after Mosley the rest of the round and again in the 11th. By then the crowd was cheering "Knock him out! Knock him out!" but Pacquiao -- bothered by a cramp in his left leg since the fourth round -- didn't have enough to finish him off.
"It wasn't my best performance," Pacquiao said. "I did my best. I did not expect this result."
The closest Mosley got to Pacquiao all night came at the beginning of the 12th round when he hugged Pacquiao before the two went about finishing their business. That took some of the fire out of Pacquiao, who didn't really go after the knockout in the final round.
Promoter Bob Arum defended putting Mosley in the ring against Pacquiao despite signs in Mosley's last two fights that his reflexes were slipping.
"Nobody can really perform against him," Arum said. "Some of these guys are pretty good fighters, but nobody in their whole experience has ever faced somebody like Pacman. Everybody is going to look the same way."
Pacquiao (54-3-2, 38 knockouts) was a 7-1 favorite and also the favorite of the crowd that gathered expecting to see another one of his thrilling performances. That he couldn't deliver was the only bad part of the night for a fighter who doubles as a congressman in his native Philippines.
It wasn't the distractions of trying to do two jobs well, Pacquiao said, but leg problems that first cropped up in his fight last November against Antonio Margarito.
"I thought Shane did a great job, he had some speed," Pacquiao said. "I couldn't move because my left leg got tight. It's a problem I've been having lately. I'm going to work on my legs in future training camps."
Mosley (46-7-1-1) said he thought he did a good job despite losing round after round, and wouldn't blame his bad performance on the fact he is 39 and has been fighting ever since he was a child.
Mosley was tentative from the opening bell, moving backward and unwilling to engage Pacquiao. With good reason, because a left hook by Pacquiao found its mark with a minute left in the third round and put Mosley on the canvas for only the third time in his 18-year pro career.
Mosley was up at the count of five, and managed to survive the final minute of the round despite Pacquiao's best efforts to take him out. Pacquiao didn't come close to stopping him after that, but landed enough punches to the head that Mosley's right eye was nearly swollen shut in the late rounds and the left side of his face was puffy, too.
Pacquiao pressed the fight most of the night, but he, too, didn't take many chances, which trainer Freddie Roach said was because of the muscle cramp that his corner tried to massage between rounds.
"He had no leverage to move after that," Roach said. "It was a very gutty performance in my mind."
Perhaps, but the sellout crowd of 16,412 came to see more, and booed repeatedly in the late rounds. The boos were directed at Mosley, not Pacquiao, but it was clear early on this would not be a classic fight.
Mosley came into the ring with the song "Mama Says Knock You Out," but what would have been more appropriate if he had found a song called "Mama Says Don't Knock Me Out."
Mosley fought as if trying to protect his legacy of having never been stopped and, if that was his strategy, it succeeded. But it made for a lackluster fight and did nothing to burnish the legacy that the Filipino champion has built with 14 straight wins over the last six years -- including some over some of the biggest names in the game.
Pacquiao, who wore yellow gloves as a symbol of solidarity in the fight against poverty in his country, made a minimum of $20 million for the fight. Mosley, who has now won only two of his last six fights, was guaranteed $5 million.