Pacquiao faced Agapito Sánchez in a unification match on November 10, 2001, at the Bill Graham Civic Auditorium in San Francisco, California as the main supporting bout of Floyd Mayweather Jr. vs. Jesús Chávez.

The bout ended in the sixth round under the recommendation of the ringside physician to stop the fight as Pacquiao was unfit to continue due to the cuts inflicted by Sanchez's repeated headbutts.

[39] Pacquiao knocked out Jorge Eliecer Julio in the second round on June 8, 2002, at The Pyramid in Memphis, Tennessee as the main supporting bout of Lennox Lewis vs. Mike Tyson fight.

[42] On November 24, 2003, the then Philippine President Gloria Macapagal Arroyo conferred on Pacquiao the Presidential Medal of Merit at the Ceremonial Hall of Malacañang Palace for his knockout victory over the best featherweight boxer in the world.

[47] On September 10, 2005, Pacquiao knocked Héctor Velázquez out in six rounds at Staples Center in Los Angeles to capture the WBC International super featherweight title, which he went on to defend five times.

[48] On July 3, 2006, the day after winning the fight against Larios, President Gloria Macapagal Arroyo personally bestowed the Order of Lakandula with the rank of "Champion for Life" (Kampeon Habambuhay) and the plaque of appreciation upon Pacquiao in a simple ceremony at the Presidential Study of Malacañang Palace.

On June 29, 2007, Top Rank and Golden Boy Promotions announced that they agreed to settle their lawsuit, meaning the long-awaited rematch with Marco Antonio Barrera would occur despite Pacquiao being the top-ranked contender for Juan Manuel Márquez's WBC super featherweight title.

[56] Guzmán went as far as to directly call out Pacquiao at the post-fight press conference of the Pacquiao–Barrera rematch in front of the crowd at the Mandalay Bay Events Center's media room in Las Vegas.

[67] On December 6, 2008, Pacquiao moved up to the welterweight division to face the six-division world champion Oscar De La Hoya at the MGM Grand Garden Arena, in a fight called "The Dream Match".

Although Pacquiao went into the fight widely recognized as the leading pound-for-pound boxer in the world, some boxing pundits had speculated that 147 pounds could be too far above his natural weight against the larger De La Hoya.

[75] On May 2, 2009, Pacquiao fought at light welterweight for the first time against Ricky Hatton at the MGM Grand Garden Arena, in a fight billed as "The Battle of the East and West."

However, with less than ten seconds remaining in the round, Hatton was knocked out cold by a sharp left hook, prompting the referee to award Pacquiao the win by knockout at 2:59.

[88] On November 20, 2009, in a simple rites at the Quirino Grandstand, President Macapagal-Arroyo conferred Pacquiao the Order of Sikatuna with the rank of Datu (Grand Cross) with Gold distinction (Katangiang Ginto) which usually bestowed upon foreign diplomats and heads of state.

[104] Counting complimentary tickets delivered to sponsors, media outlets and others, the Dallas fight attracted 41,843,[104] well short of the 50,994 that was previously announced,[105] but still an epic number for boxing.

It was later reported that Golden Boy Promotions CEO Richard Schaefer and Top Rank Chief Bob Arum worked out a "super fight" between Manny Pacquiao and Floyd Mayweather Jr..

[107] On June 12, 2010, the President of Golden Boy Promotions, Oscar De La Hoya, stated during an interview with Univision that the deal for the fight was very close and the negotiation process has been very difficult.

[115][116] Floyd Mayweather Jr., after the second negotiation had been officially declared off, told the Associated Press that he had fought sixty days ago and that he was not interested in rushing into anything and was not really thinking about boxing at the moment.

[119] Prior to the fight, Pacquiao's team demanded to the Texas officials to test Margarito for banned substances after a weight loss supplement, reportedly Hydroxycut, was found in his locker.

[124] On May 7, 2011, Pacquiao successfully defended his WBO welterweight title against three-division world champion Shane Mosley via lopsided unanimous decision at the MGM Grand Garden Arena.

Rapper LL Cool J performed as Mosley first entered the arena, while vocalist Jimi Jamison of the rock band Survivor sang "Eye of the Tiger" as Pacquiao approached the ring.

[134] On February 5, Bob Arum announced Timothy Bradley as Pacquiao's next opponent on June 9 for his WBO welterweight title, after another failed negotiation attempt with Floyd Mayweather Jr. on Cinco de Mayo.

[151] Boxing fans were surprised when Pacquiao and his camp chose to challenge Timothy Bradley in a rubber match on April 9, 2016, at the MGM Grand Garden Arena in Las Vegas for the WBO International welterweight title.

On July 13, Pacquiao responded to rumors that he intends to take a leave of absence from the Philippine Senate for an upcoming bout – as stated by Top Rank Promotions head, Bob Arum.

"[162]On July 11, Arum said that Pacquiao will return to the ring sometime in the fall, likely either on October 29 or November 5, in the main event of a pay-per-view card staged in Las Vegas and televised by HBO.

[164] Pacquiao adviser Michael Koncz said in a report that the southpaw, while committed to politics, is happiest when he is in the ring: "Manny's primary concern and obligation is to fulfill his senatorial duties.

[166][167] Pacquiao made the confirmation after a two-hour meeting with Top Rank's Bob Arum and Canadian adviser Michael Koncz held in Manila on August 7, that he agreed to fight Vargas.

[185][186][187][188] Speaking to Bob Arum on March 1, Pacquiao's adviser Michael Koncz confirmed the fight would take place on May 19 in the United States which means it would be a Friday night PPV and May 20 in the Middle-East.

[263] On May 21, 2021, Pacquiao made an announcement on his social media that he would return to the ring on August 21 in Las Vegas to face undefeated unified WBC and IBF welterweight champion Errol Spence Jr. on Fox PPV.

[277] On August 20, 2002, Pacquiao faced former WBA super bantamweight champion Jesus Salud in an exhibition match in Honolulu, as one of the undercard of Gerry Peñalosa vs. Seiji Tanaka.

[282] At a June 10, 2024 Tokyo press conference, it is reported that Manny Pacquiao and Chihiro Suzuki signed a three-round exhibition fight on July 28 in Saitama Super Arena.