Ali, a so-called 13-1 underdog with some oddsmakers prior to the bell, won on scores of 115-113, 116-112 and 115-113, capturing Cotto's WBO Junior Middleweight title in the process.
Post fight Miguel Cotto would go on to say that he picked up a bicep injury in round seven of the contest, but reaffirmed that this would be his last fight and looks forward to spending more time at home with his family.
Round 6 saw Cotto deliver a right hook that sent Ali flying to the ropes, reminding the younger fighter whose goodbye party it was.
Others, Ali suspects, still won't respect his upset victory over Miguel Cotto on Saturday night at Madison Square Garden.
"Something happened to my left biceps but I don't want to make excuses, Sadam won the fight".
No doubt there was a few teary eyes in the house at Madison Square Garden this weekend, as one of its most famed fighting sons of recent memory made his 10th and final appearance at the iconic venue.
"Thank you for supporting me at every opportunity", Cotto told his fans. A right hand by Ali staggered Cotto in the second round, as did a left hook in the fourth round. "They could have taken an easier fight if they wanted to".
Perhaps sensing that the judges might gift Cotto a couple of rounds, Ali went for broke in the final two frames.
"I knew I had to do something, or he would have dug in", said Ali, who improved to 26-1 with 14 knockouts.
Pre-fight many within the industry were critical of this fight, stating it would be nothing but routine for Cotto.
Cotto had received a thunderous ovation when he entered the ring, and they were chanting his name as he left, proud but defeated.
While Cotto double- and triple-jabbed to get inside, Ali stood his ground and fired back, catching Cotto with surprisingly clean punches during the early rounds. "I have been training since I was 8 years old, and I am glad I got this win at MSG, in my hometown".
Unless Cotto yields to some unforeseen urge to withdraw his pledge to stay retired, his legacy shall forever remain beyond reproach or cause for sympathetic tsk-tsks.
Cotto's trainer, the great Freddie Roach, believes his fighter would have been up for such a challenge against either man but is now ready to deal with what is in front of him.
But Vargas, 27, also landed dozens of body blows and rarely allowed the 30-year-old Negrete inside. Sadam won the fight. Yet, it was Vargas who looked the worse when they left the ring. He fought gamely, trying his best to apply pressure and bore his way in with compact power shots, and did make this a competitive farewell encounter, even rocking Ali with a straight right in the 6th.
"It's taken me five years to get here, and I'm cherishing this moment for me and for Puerto Rico", Acosta said.