Mayweather, who was leading on judges scoreboards from first to fifth rounds, got a beating from Cotto on the sixth round and followed it up on the seventh and eighth rounds for a three-round winning streak.
Mayweather, who appeared dazzled by Cotto's relentless assault, started with his own flurry of punches in the eighth round which found their mark on Cotto, who did not show much action on this particular round.
Starting on the ninth round, Mayweather showed his superiority in style and stamina by scoring at will until the end of the last round
Both Judges Dave Moretti and Patricia Morse Jarman score the fight at 117-111 while Robert Holye scored it at 118-110, all for the winner Floyd Mayweather, Jr
Early this year, Mayweather was trying to lure pound for pound king Manny Pacquiao to a fight scheduled for May 5, but negotiations for what could have been the biggest boxing event of the year fell through because of disagreement on purse sharing.
Mayweather offered Pacquaio at least $40 million guaranteed purse without a single share in pay-per-view (PPV) receipts but the Filipino boxing star rejected it saying it was an "embarrassing" offer.
Mayweather admitted on HBO "Face Off with Max Kellerman" (h/t Yahoo! Sports) that Cotto is a tough opponent
, saying he considered the Puerto Rican as undefeated in his own boxing career.
"We choose Miguel Cotto because he's solid," Mayweather told Kellerman. "We want tough competition; he's one of the best fighters out there. I look at Miguel Cotto as an undefeated fighter because he faced Pacquiao, but Pacquiao caught him at a catch weight. He wasn't the best Miguel Cotto. He was drained. He wasn't hydrated. Antonio Margarito was a guy who was cheating. I want him to be comfortable and feel good when we meet and go into this battle."
Meanwhile Pacquiao has chosen Palm Spring boxing star Timothy Bradley for his June 9 fight, also at the MGM Grand Garden Arena.
With his impressive win over Cotto, Mayweather has successfully preserved his unblemished record in his professional career with 43 wins without a single loss.
Mayweather is scheduled to serve a 90-day jail term for charges stemming from his assault on his girlfriend, who is the mother of his two children, which happened in September 2010.