As always, there should be some fireworks between the two historic boxers.
After winning a controversial decision against Marquez in November 2011, Pacquiao lost a controversial decision to Timothy Bradley, Jr. in June.
Marquez defeated Serhiy Fedchenko via unanimous decision in April.
In the undercard, Yuriorkis Gamboa returns to the ring to face Michael Farenas for the vacant interim WBA super featherweight title, Miguel Vazquez goes up against Mercito Gesta for the IBF lightweight title and up-and-comer Javier Fortuna hopes to dominate Patrick Hyland for the interim WBA featherweight title.
Read on for a breakdown of the fights. Each fight will be updated as it concludes.
Yuriorkis Gamboa (21-0, 16 KO) vs. Michael Farenas (34-3-4, 26 KO)
Yuriorkis Gamboa is returning after a 15-month hiatus, last seen defeating Daniel Ponce de Leon.
The 30-year-old has a perfect 21-0 record and is a big name in the U.S. based on numerous fights on television. He has decided to move up to super featherweight (130 pounds), where he will probably have no trouble winning based on the competition.
Michael Farenas will be the challenger. The 28-year-old Filipino has power, which his team has claimed will help him against Gamboa's questionable chin.
On the other hand, Farenas has never fought anyone of Gamboa's caliber. He fought Japan's Takashi Uchiyama to a technical draw in July, but Gamboa is still in another class.
Miguel Vazquez (32-3, 13 KO) vs. Mercito Gesta (26-0-1, 14 KO)
Miguel Vazquez is a top lightweight, but his lackluster performance against Marvin Quintero in October gave a lot of people pause and hurt his reputation.
Vazquez was guilty of not being aggressive enough in that fight despite having the tools and the opponent to do so, and his victory didn't seem like much of a victory at all, but more a long, drawn-out process.
Vazquez's three losses have come to Timothy Bradley, Jr. and Canelo Alvarez (twice). He knows what he's doing, and he's had some big wins in his career.
Mercito Gesta won't be an easy fight despite his lack of competition throughout the years. He is a confident fighter who won't back down and has an aggressive style in the ring. He's a strong boxer who fights well. If Vazquez takes him lightly, there's no telling what could happen.
But Vazquez's experience in the ring against tough opponents gives him an advantage here. He's also likely to come out more aggressively than he did against Quintero.
Javier Fortuna (20-0, 15 KO) vs. Patrick Hyland (27-0, 12 KO)
Javier Fortuna is beginning to garner some buzz after some convincing victories over Yuandale Evans and Cristobal Cruz over the past year.
The 23-year-old knocked out Evans in less than two minutes in April and followed that up with a second-round knockout of Cruz in July despite Cruz being a former IBF and IBO featherweight champion.
The first thing you notice is Fortuna's speed and agility inside the ring. He appears to glide at times. He also has the power to go along with it, and there are many who believe he's destined for big things moving forward.
Patrick Hyland doesn't figure to have much of a chance in this affair. He's fought much weaker competition throughout his career, and he doesn't have the tools of Fortuna. On top of that, Fortuna is rising like a rocket at the present moment, and Hyland has picked a bad time to fight the buzz-worthy Dominican.
Main Event: Manny Pacquiao (54-4-2, 38 KO) vs. Juan Manuel Marquez (54-6-1, 39 KO)
Juan Manuel Marquez has historically been Manny Pacquiao's greatest rival. He may have actually won their third fight in November 2011 if it wasn't for a controversial call by the judges to award Pacquiao the victory.
He's an aggressive but smart boxer who has a toughness and a chin hardened by years of fighting against imposing figures, including Floyd Mayweather, Jr. in September 2009 (a loss via unanimous decision).
Stylistically, the 39-year-old Mexican has always given the Filipino problems, and that doesn't figure to change this time around.
Of course, Pacquiao is one of the greatest boxers in history, but it's also clear he can't fight at the same furious pace, which is understandable given his resume.
Still, he was more aggressive against Timothy Bradley, Jr. in June, and I expect him to be more aggressive against Marquez in their fourth fight.
Javier Fortuna used his athleticism to out-box brawler Patrick Hyland Saturday night to earn a unanimous decision victory. With the win, the 22-year-old now holds the interim WBA featherweight title.
This fight came down to activity. Hyland can only fight one way, but Fortuna was more efficient with his activity. Hyland tried to land a few key counterpunches, but Fortuna was always waiting with a response.
The first few rounds were rather slow. Fortuna picked up the pace starting in Round 4, and he didn't look back from there. His work rate allowed him to land many more punches, failing to let Hyland have any room to maneuver.
In Round 9, Fortuna seized control by cutting Hyland above his right eye. That turned the tide, giving the judges the only real sign of damage on either fighter. Hyland couldn't answer that in the bout's final three rounds, and he suffered on the scorecards because of it.
Fortuna has to be happy with the belt around his waist, but this young fighter has brighter days ahead of him.
Miguel Vazquez retained his IBF lightweight championship with ease Saturday night, dominating Mercito Gesta for 12 rounds.
This bout wasn't even close. It was so bad that Jim Lampley, Larry Merchant and Roy Jones, Jr. were basically begging the fight to end over the air.
Vazquez landed three times as many punches as his opponent, threw more and hit Gesta at a higher percentage than Gesta hit him. He put on a clinic, steering his opponent around the ring with ease.
This was Gesta's first real challenge so far in his career, and it was obvious. He couldn't cut off the ring, allowing Vazquez to dictate the tempo and style of the fight. Against a fast-moving, cagy fighter like Vazquez, that's a recipe for defeat every single time.
Vazquez was impressive Saturday night, but this was a mismatch. It will be interesting to see who he fights next as he looks to hang on to his championship belt.
Yuriorkis Gamboa won the interim WBA super featherweight title with a dominant performance over Michael Farenas Saturday evening.
The night's final undercard bout was the most exciting of the bunch, but Gamboa was in control for most of the night. He scored a knockdown in Round 2 and another in Round 7, putting Farenas in a tough spot entering the match's final rounds.
In the ninth round, Farenas shocked everyone though. Gamboa was in position to end the match, but left himself wide open to a straight punch from Farenas. Farenas connected and put Gamboa down on the mat.
That knockdown wasn't enough to even things up for Farenas, but it was surprising nonetheless. Gamboa was more active, and he landed more punches. Despite a 15-month hiatus from the ring, he proved himself as the match's best all-around fighter.
After watching his comeback, it will be interesting to see where Gamboa goes from here. His combination of speed and power will make him an interesting matchup for anyone.
The main event provided a thrilling end to the night and produced a massive upset and an incredible knockout. Juan Manuel Marquez dropped Manny Pacquiao at the end of the sixth round to beat Pac-Man for the first time in four fights.
Pacquiao was the aggressor in the early rounds, and was having a significant amount of success with his straight left hand. Had he avoided a knockout, Pacquiao likely would have won the fight.
But Marquez was able to land the first major blow of the fight. In the third round, he provided fans in Las Vegas with a rare sight when knocked Pacquiao to canvas.
But the Filipino wasted little time before regaining the advantage in the fight. He used his infamous straight left hand to earn his first knockdown in the fifth round.
The momentum was clearly moving in Pacquiao's favor, but Marquez used a masterful counterpunch to deliver the knockout blow. It was a brutal punch with massive implications that will not be forgotten soon.