But was his powerful right hand blow the final end to their historic book? Or is there another chapter that has yet to be written?
Following the fight, there were some intriguing comments that hinted to a fifth fight in the future.
Here is what was said following the fight, according to Dan Rafael of ESPN.
"A fifth fight? Why not?" Top Rank promoter Bob Arum said. "Have you seen a more exciting fight in years?"
Pacquiao, who went to the hospital after the fight to be checked out, echoed his promoter.
"Why not?" Pacquiao, who earned at least $26 million, said after regaining his senses. "Yes, it's a good fight. I was just starting to feel confident because I thought I got him. If they give us a chance, we'll fight again. I'm gonna take a rest and then I am coming back to fight."
So that's it. They will most likely be fighting for the fifth time. It's laughable from the sport of boxing's perspective, but it makes the most sense for both fighters.
Pacquiao needs a victory before potentially heading into a fight with Floyd Mayweather. We don't want to see a loser of back-to-back fights go up against Mayweather in what would be deemed the fight of the century.
Would you want to watch a 5th fight between Pacquiao and Marquez?
We want to see two guys on top of their game go at it, and while boxing missed its chance to have this happen, they can still make it as watchable as possible. I'm sure people would still buy the pay-per-view and stream it from their computers, but it would make the fight better if Pac-Man can get back into the win column.
On the other side of the fence is Marquez.
Marquez would be getting one of the best paydays of his career at age 39. How do you turn that down?
The most logical decision following the knockout would be for these two fighters to go at it once again. Maybe Timothy Bradley could get his shot at Floyd Mayweather in the meantime.
The scene would be set perfectly for a Mayweather vs. Pacquiao fight if both came out on top.
Judging how Pacquiao has been performing lately, though, don't be surprised if he fails to live up to expectations for the third straight time.