(CNN) -- With a crushing right hand, Juan Manuel Marquez knocked out Manny Pacquiao in the sixth round of a non-title bout in Las Vegas late Saturday, scoring a definitive victory after three previous bouts that ended in close judgments.
The fight came to an end 2:59 into the sixth round, after Juan Manuel Marquez landed a right hand to Manny Pacquiao's face, knocking him cold late Saturday at the MGM Grand Garden Arena.
Pacquiao went down face-first and lay motionless for a while, possibly unconscious, before eventually sitting up. It was called a technical knockout and Marquez declared the winner.
Pacquiao shook Marquez' hand after getting back on his feet.
The loss to his arch rival comes as a second severe blow to Pacquiao's career this year. He lost his title to American Timothy Bradley in June.
Manny Pacquiao and Juan Manuel Marquez went head-to-head for the first time in the featherweight division in 2004, a controversial bout which ended as a draw. The result stood, despite one judge admitting he had made a mistake when scoring a round 10-7 to Pacquiao rather than 10-6. They stepped back into the ring in a super featherweight fight in 2008, pictured above.
Pacquiao vs. Marquez
A history of Pacquiao-Marquez
Manny Pacquiao's greatest hits
Juan Manuel Marquez's greatest hits
Saturday's fight was originally scheduled for 12 rounds. Both fighters scored a knock-down earlier in the fight with Marquez sending Pacquiao flying onto his back and Pacquiao tipping Marquez enough off of his feet to cause one of his gloves to touch the mat.
Former presidential hopeful Mitt Romney was at ringside with his wife Ann and shook Pacquiao's hand before the match to wish him success. Pacquiao is an elected congressman in his native Philippines.
Actor Steven Seagal and Basketball legend Earvin "Magic" Johnson could be seen at the match, and former heavyweight boxing champion Mike Tyson tweeted that he was also in attendance.
It's a rare case when it takes a fourth fight to satisfy the fighters, the fans and the press.
Boxers often have other rivals to battle, and younger fighters come along deserving their shots.
But for Pacquiao (now 54-5-2, 38 KOs) and Marquez (now 55-6-1, 40 KOs), their legacies required at least one more battle in the ring.
Pacquiao has, in the eyes of the judges, won two of the previous matches. The first was ruled a tie. He believes he won all three. Marquez fervently believes he won all three.
At a press conference announcing the fight, Pacquiao used his thumb to scratch into the tablecloth, "We need to win by knockout" for his trainer Freddie Roach to see.
"I said, 'Yes, we do,'" Roach said. He didn't think it likely that judges would hand a third decision victory to his fighter.
Marquez has also said that he believed he needed to score a knockout to put all doubts to rest.
Pacquiao's prior opponent gave him a taste of what Marquez has felt during the reading of the scorecards for their battles. It appeared Pacquiao dominated Bradley in a 12-round welterweight title fight in June, but he lost the decision on two of the three judges' scorecards.
Bradley walked off with the WBO belt.
Public sentiment and the opinion of sports media on Marquez' and Pacquiao's previous bouts have fallen mostly in the middle.
What everyone agrees on is that the fights have been great. Pacquiao has come hard after Marquez, who has counter-punched superbly. Pacquiao has knocked Marquez down four times, three of which came in the first round of the first fight.
Had the referee stopped the fight, as they often do after a boxer falls three times, the trilogy would have been a quick one-night stand, or one-night fall, as it were.
Now the two fighters are forever linked, and there is a clear victor.
CNN's Jill Martin contributed to this report.
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Pacquiao was given the fight and subsequently took Marquez's super featherweight title, with a knockdown in the third round proving the difference after all other rounds were scored equal.
Controversy once again reigned when the two fought for a third time in in a welterweight bout in November 2011.
Pacquiao was awarded another points win, a decision greeted by boos from the Las Vegas crowd.
Marquez knocked out Pacquiao in the sixth round Saturday night in Las Vegas. Pacquiao lay motionless for a while, before eventually sitting up. With the technical knockout, Marquez was declared the winner.
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