Mayweather troubled his Mexican opponent throughout the contest
Floyd Mayweather Jr returned to the ring for the first time in 21 months with a unanimous points victory over Juan Manuel Marquez in Las Vegas.
Mayweather, who announced his retirement after beating Ricky Hatton in 2007, dominated his five-time, three-weight world champion opponent.
The American knocked down Marquez in the second round, then peppered him with damaging shots to remain unbeaten.
Marquez stepped up two weight classes for the non-title welterweight fight.
And that step up told as 32-year-old Mayweather dominated all 12 rounds against his smaller opponent with his left jab and agile movement, improving his career record to 40-0 with 25 knockouts.
Mayweather, who had a significant weight and reach advantage, was a heavy favourite going into the bout at the MGM Grand Garden Arena and floored Marquez, 36, with a stinging left hook in the second round.
And he showed no signs of rust after his lengthy stint away and controlled the pace of the fight with his lightning hand and foot speed, rock-solid defence and a series of telling combinations.
Marquez, who has fought most of his career at featherweight but is a reigning world champion at lightweight, suffered a bloody nose as Mayweather landed several hard shots late in the sixth.
He's too fast. When I hit him he laughed but I knew he felt my punches
And whenever he appeared to land a combination, Mayweather simply backed away with a grin.
Mayweather ended the 11th round by landing a crunching right hook and maintained control until the final bell sounded to end the 12th.
"I've been off for almost two years but it felt really good to be back. I was happy with the victory but I know I can get better, " said Mayweather, who gained one-sided verdicts from all three judges - by 118-109, 120-107 and 119-108.
But he paid tribute to his "tough as nails" opponent, adding: "He was a great little big man. I threw a hell of a shot that dropped him, and then he got back up and kept fighting. He's a tough guy."
Marquez, who had never before fought above 135 pounds and was four pounds lighter at Friday's weigh-in, said: "He surprised me with the knockdown. He hurt me in that round but not at any other time."
He added: "I don't want to make excuses but the weight was the problem.
"He's too fast. When I hit him he laughed but I knew he felt my punches. I did the best I could do."
Eighteen months ago, Marquez lost a narrow decision to Manny Pacquiao - who is believed to be Mayweather's first choice for his next bout.
The prospect of a Mayweather-Pacquiao fight would be hugely appealing, but it was 'Sugar' Shane Mosley, another potential opponent, who demanded the attention of Mayweather in the ring immediately after the fight, with officials forced to separate the two.
Mayweather did not comment on a fight with Mosley, but his uncle and trainer, Roger Mayweather, earlier said Mosley would produce "a better fight than Pacquiao".
Meanwhile, Indonesia's Chris John retained his WBA featherweight title with an unanimous decision over Rocky Juarez on the Mayweather-Marquez undercard and Australian Michael Katsidis took the interim WBO lightweight title with a split-decision win over Vicente Escobedo.
In Germany, local favourite Sebastian Sylvester became the new IBF world middleweight champion after winning the title decider against Giovanni Lorenzo of the Dominican Republic.