Not content with just winning in the ring, Pacquiao also set about making his mark in politics.
But after his stunning loss to Juan Manuel Marquez in Las Vegas on Saturday, the 34-year-old is facing some of the toughest questions of his remarkable 17-year career: does his future lay in boxing, politics, show business, religion, or perhaps there's even a new challenge on the horizon?
"Being the king of boxing, being the highest paid athlete in boxing ... it goes with the territory," boxing analyst Ed Tolentino said. "For Pacquiao, the fame was too much to handle. There was just too many things on his plate other than boxing."
The distraction was costly for Pacquiao, who trained for two months, compared to 4 1/2 for Marquez.
During that time the Mexican bulked up and became more muscular to withstand the blows from Pacquiao that proved so damaging in their three previous encounters.
Pacquiao grew up a survivor and fighter, overcoming poverty and cut-throat competition in a country where half of the population lives on $2 a day and 3,000 leave for jobs overseas every day.
He left high school to work as a baker and a construction worker to earn money for his mother and siblings after his father left them. As a scrawny teenager, he was a stowaway on a ship that took him from his southern hometown of General Santos City to the capital, Manila, where he took up boxing while working as a labourer.
After finding success in local bouts, Pacquiao began his international career in the late 1990s. In the next decade, he became a household name by clinching eight world titles in eight weight categories. At home, he was declared a hero, "the people's champ" — an inspiration to the legions of the poor, and the man the rich and powerful wanted to rub shoulders with.
As the titles, honours and money started pouring in, so did distractions.
Politicians, minor actors and an assortment of hangers-on formed his huge entourage.
"You only need a Ferris wheel and his training camp would have been a circus," Tolentino said.
In a nation where celebrities, money and politics equal a winning formula, Pacquiao played his card by running for Congress in 2007, but lost.
The most popular face in town, he turned to crooning his own songs. His picture endorsed countless products. He's a regular on TV, and hosts his own show. He's made a movie. Another passion is cock fighting, a traditional past time in the Philippines.
He was Pacquiao Inc.
Showbiz "takes a lot of time, a lot of energy. You have to prepare for these shows," said boxing commentator Ronnie Nathanielsz. "(Pacquiao) loses focus because he has so many things to worry about and attend to."
Pacquiao was elected to Congress from his southern Sarangani province in 2010, and has announced he will run for re-election next year. Taking a cue from his political allies, he appears to be building a political organization, with his wife, Jinkee, running for vice governor, and younger brother, Rogelio, for congress in neighbouring South Cotabato province.
In the meantime, he promised to clean up his act: no more gambling, drinking and womanizing, and took up preaching the Bible. Some called it a public relations stunt for a budding politician, but Pacquiao insisted it was for real.
"To those who think that way, let us leave them be. I will pray for them. Even Jesus Christ, even after he performed miracles, no one believed him, what more for a sinner like me," he said, adding he did not want to be a pastor but share how "the Lord changed my life."
Then came the first blow: a controversial decision awarding his June fight to Timothy Bradley. Questions arose if Pacquiao was showing the wear of 17 years in the ring, and whether the distractions catching up with him.
Saturday's loss to Marquez, whom he had beaten twice and drawn once, only made the question more urgent, although Pacquiao made no mention of a possible retirement.
"Among boxers, they don't have the word retirement in their dictionary. It's so hard to admit that all of sudden it's over, especially for Pacquiao," Tolentino said.
"His demotion was from the penthouse to the doghouse," he added. "I think really there has to be a lot of soul searching. ... He has to consult his family, his real entourage."
Associated Press writer Oliver Teves contributed to this report.