On June 17, 2000, Mosley met De La Hoya in Los Angeles for the WBC and IBA Welterweight titles. After twelve rounds, Mosley emerged with a split decision victory. During the fight neither man was in danger of going down, but both had badly swollen faces at the end and De La Hoya was bleeding from the nose for several rounds. Mosley earned a minimum of $15 million, while De La Hoya was guaranteed $35 million. It was later that Mosley was accused of using illegal performance enhancing drugs prior to his 2003 bout with Oscar De La Hoya. He ran a successful string of defenses of his Welterweight title (he vacated his title after the fight), but against three unheralded fighters. When he finally did step up his competition, it was against former Olympian Vernon Forrest. Early in the second round, the fighters clashed heads and both staggered backward as referee Steve Smoger called time. Mosley sustained a cut on the hairline. When action resumed, Forrest knocked Mosley down twice in the round. It was the first time Mosley had ever been down in a bout. The final scorecards read 115-110, 117-108, 118-108, in favor of Forrest. They had a rematch six months later at Conseco Fieldhouse in Indiana, and Mosley once again lost by a unanimous decision. On February 8, 2003, Mosley's bout with former IBF world Light Middleweight champion Raúl Márquez ended in a no contest when Mosley accidentally head butted Marquez twice in round three, which caused two very bad cuts above the eyes of Marquez. He and De La Hoya faced each other for the second time on September 13, this time with De La Hoya's WBC and WBA Light Middleweight belts on the line. Mosley defeated De La Hoya by a close 12 round unanimous decision, and joined the exclusive group of world boxing champions that have reigned in three or more divisions. Mosley testified in 2003 that he injected himself with the notorious doping agent EPO as he prepared for his Light Middleweight title fight against Oscar De La Hoya, according to grand jury transcripts and doping calendars. On March 13, 2004, Mosley lost his WBC and WBA world Light Middleweight titles in a unification bout with IBF Jr. Middleweight champion Winky Wright, by a unanimous twelve-round decision. On November 20, Mosley and Wright fought their rematch, and although it was scored much closer by the three judges (115-113 twice for Wright and a 114-114 tie), Mosley lost by a twelve-round majority decision. On September 17, he beat another previously undefeated fighter, Jose Luis Cruz, by a ten-round decision. Mosley then defeated Fernando Vargas on February 25, 2006 by TKO in the tenth round at the Mandalay Bay Resort and Casino, due to a massive swelling which closed Fernando's left eye. At the time of the stoppage, Mosley was winning on two scorecards 86-85, while Vargas held an 86-85 advantage on the other scorecard. A rematch was announced almost immediately. Mosley defeated Fernando Vargas in the rematch on July 15, 2006. Mosley dominated Vargas from start to finish, eventually ending the fight via a sixth-round TKO. Shane defeated Luis Collazo on February 11, 2007, with a unanimous decision after 12 rounds, knocking Collazo down once, to capture the WBC interim Welterweight title.
Mosley and undefeated WBA welterweight Champion Miguel Cotto met on Nov. 10, 2007, at Madison Square Garden in a fight broadcasted on HBO Pay-Per-View. Cotto beat Mosley in a close fight. Soon after that match, Mosley was scheduled to face Zab Judah in a Welterweight bout in Las Vegas, Nevada on May 31. Due to an arm injury suffered by Judah, the fight was cancelled. Mosley-Mayorga was originally scheduled for Oct. 11 at the Staples Center in Los Angeles, Golden Boy Promotions CEO Richard Schaefer and Mosley's wife and advisor, Jin Mosley, told ESPN.com. On July 18, 2008, it was reported on ESPN.com's quick hits that The fight between Mayorga and Mosley was moved to the Home Depot Center in Carson, California and set for September 27 because of the Pavlik-Hopkins fight agreement for October 18 on HBO PPV. And the good news for fight fans was that the Mayorga-Mosley bout was not to be on HBO PPV, instead it was shown on HBO at no cost. Shane Mosley Stopped Ricardo Mayorga with one second left in the 12th round of their junior middleweight bout, Mosley led by one point on judge Nelson Vasquez's scorecard and five on Tony Crebs' entering the 12th round. Mayorga had a one point lead on judge Pat Russell's card. The Associated Press had "Sugar" Shane Mosley ahead by three points entering the 12th. Prior to one of the biggest fights of his career, Mosley began training with Naazim Richardson. Mosley regained the WBA Welterweight "Super" championship from Antonio Margarito on January 24, 2009 at the Staples Center in Los Angeles, California. Mosley, now 37 years old, came in to the fight as a 4-1 underdog with the bookies after Margarito had spectacularly stopped Cotto 6 months earlier. Prior to the bout nobody gave Mosley a chance of prevailing- everybody believing that Margarito was too strong and that Mosley was too old. The conventional wisdom was that this was a mismatch, which would end in a brutal retirement-forcing stoppage for Sugar Shane. A comparison of their last fights- the aforementioned destruction of Cotto by Margarito and a last-gasp knockout by Mosley in a hard twelve round struggle against Mayorga- did not bode well for Sugar Shane. Some predicted a massacre. And it was - only it was Margarito that was ruthlessly clubbed about the ring, unable to land any meaningful shots. On 1 May 2010 Mosley fought undefeated Floyd Mayweather. Boxing purists had called for the fight for over ten years. On the night Mosley stunned Mayweather with two right-hand shots in the second round. Mayweather recovered well and dominated the remainder of the fight with superior hand speed, eventually winning a wide decision on the scorecards to hand Mosley the sixth defeat of his professional career. On May 22, 2010 Shane Mosley was stripped of his WBA "Super" Welterweight Title, which in turn made "Regular" champion Vyacheslav Senchenko the sole WBA titlist in the welterweight division. Mosley fought Sergio Mora on September 18 at the Staples Center in Los Angeles. The bout ended up in a split draw. Scores (Mora 115–113, Mosley 116–112, 114–114).On May 7, 2011, Mosley lost the fight to Manny Pacquiao for the welterweight title on the MGM Grand in Las Vegas. Due to Mosley's defeat, Pacquiao may be looking at a November matchup against either Floyd Mayweather, Victor Ortiz or a third fight with Juan Manuel Marquez.
Mosley and undefeated WBA welterweight Champion Miguel Cotto met on Nov. 10, 2007, at Madison Square Garden in a fight broadcasted on HBO Pay-Per-View. Cotto beat Mosley in a close fight. Soon after that match, Mosley was scheduled to face Zab Judah in a Welterweight bout in Las Vegas, Nevada on May 31. Due to an arm injury suffered by Judah, the fight was cancelled. Mosley-Mayorga was originally scheduled for Oct. 11 at the Staples Center in Los Angeles, Golden Boy Promotions CEO Richard Schaefer and Mosley's wife and advisor, Jin Mosley, told ESPN.com. On July 18, 2008, it was reported on ESPN.com's quick hits that The fight between Mayorga and Mosley was moved to the Home Depot Center in Carson, California and set for September 27 because of the Pavlik-Hopkins fight agreement for October 18 on HBO PPV. And the good news for fight fans was that the Mayorga-Mosley bout was not to be on HBO PPV, instead it was shown on HBO at no cost. Shane Mosley Stopped Ricardo Mayorga with one second left in the 12th round of their junior middleweight bout, Mosley led by one point on judge Nelson Vasquez's scorecard and five on Tony Crebs' entering the 12th round. Mayorga had a one point lead on judge Pat Russell's card. The Associated Press had "Sugar" Shane Mosley ahead by three points entering the 12th. Prior to one of the biggest fights of his career, Mosley began training with Naazim Richardson. Mosley regained the WBA Welterweight "Super" championship from Antonio Margarito on January 24, 2009 at the Staples Center in Los Angeles, California. Mosley, now 37 years old, came in to the fight as a 4-1 underdog with the bookies after Margarito had spectacularly stopped Cotto 6 months earlier. Prior to the bout nobody gave Mosley a chance of prevailing- everybody believing that Margarito was too strong and that Mosley was too old. The conventional wisdom was that this was a mismatch, which would end in a brutal retirement-forcing stoppage for Sugar Shane. A comparison of their last fights- the aforementioned destruction of Cotto by Margarito and a last-gasp knockout by Mosley in a hard twelve round struggle against Mayorga- did not bode well for Sugar Shane. Some predicted a massacre. And it was - only it was Margarito that was ruthlessly clubbed about the ring, unable to land any meaningful shots. On 1 May 2010 Mosley fought undefeated Floyd Mayweather. Boxing purists had called for the fight for over ten years. On the night Mosley stunned Mayweather with two right-hand shots in the second round. Mayweather recovered well and dominated the remainder of the fight with superior hand speed, eventually winning a wide decision on the scorecards to hand Mosley the sixth defeat of his professional career. On May 22, 2010 Shane Mosley was stripped of his WBA "Super" Welterweight Title, which in turn made "Regular" champion Vyacheslav Senchenko the sole WBA titlist in the welterweight division. Mosley fought Sergio Mora on September 18 at the Staples Center in Los Angeles. The bout ended up in a split draw. Scores (Mora 115–113, Mosley 116–112, 114–114).On May 7, 2011, Mosley lost the fight to Manny Pacquiao for the welterweight title on the MGM Grand in Las Vegas. Due to Mosley's defeat, Pacquiao may be looking at a November matchup against either Floyd Mayweather, Victor Ortiz or a third fight with Juan Manuel Marquez.