The unbeaten Mayweather (43-0) was put under immense pressure early on by a relentless Cotto (37-3) but weathered the storm and finished the stronger.
Two judges gave Mayweather a 117-111 decision while another had it 118-110 for the American, who tipped his hat to tough Puerto Rican Cotto.
Worthy opponent
"You're a hell of a champion. You're the toughest guy I ever fought," he said. "You want to give the fans what they pay for and that's excitement. It comes with the territory when you fight a future Hall of Famer like Miguel Cotto.
"I had to fight hard and suck it up. I dug down and fought him back."
Mayweather began by landing stiff jabs and fast right hands, but Cotto motored relentlessly forward, bullying Mayweather to the ropes and battering his body with left hooks.
As the rounds progressed, Cotto's constant pressure seemed to be taking its toll and after the sixth Mayweather returned to his corner with a bloody nose.
In the eighth, Cotto pounded the American against the ropes but that would prove the high point for the champion as Mayweather changed strategy, employing more lateral movement and firing right hands from long range.
By the 12th, Cotto needed a stoppage to win but it was Mayweather who closed in style, rattling his opponent with combinations that buckled Cotto's knees and smiling as he evaded counter-attacks.
After the decision, Mayweather discussed a possible fight with Manny Pacquiao of the Philippines, his rival for the title of the world's best pound-for-pound fighter.
Fans have been clamouring for the mega fight, which has hit various stumbling blocks including Mayweather's insistence that Pacquiao agree to blood testing and how the revenue from the fight is to be divided. "I tried to make the Pacquiao fight and that didn't work, so I fought Miguel Cotto instead and gave the fans a great fight," Mayweather said. "I want to fight Pacquiao but he has to take the test, and I'll fight him."
Cotto said he could not have done anything more in the fight.
"The judges said I lost the fight. I can't do anything else," he said. "I have to take my defeat.
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