He responded with a right hand that ended a bizarre fight early.
Mayweather remained unbeaten and did it in emphatic fashion Saturday night, stopping Ortiz at 2:59 of the fourth round to take the piece of the welterweight title Ortiz brought into the ring.
The end came just as the two fighters emerged from a break, in which Ortiz had embraced Mayweather in the centre of the ring. As they broke, Mayweather shot out a left hand and followed it with a right that put Ortiz down in his corner.
Ortiz struggled to get up as referee Joe Cortez called an end to the fight.
"We touched gloves and we were back to fighting and then I threw the left and right hand after the break," Mayweather said. "In the ring you have to protect yourself at all times."
The round was already controversial, as Ortiz appeared to head butt Mayweather intentionally, leading Cortez to take a point away from him. After the head butt, Ortiz went to Mayweather and gave him a kiss on the cheek.
Seconds later they were in the centre of the ring ready to resume action when two punches ended it quickly.
"I took the break by the referee and I obeyed exactly as I was told," Ortiz said. "And then, boom, he blindsided me."
Mayweather was winning the fight through three rounds, dominating with speed and landing good right hands to the head of Ortiz. He won all three rounds on two ringside scorecards, and two of three on the third.
Ortiz picked up the pace in the fourth round, trying desperately to get inside Mayweather's vaunted defence. He did on occasion and was having a better round when, late in the round, he appeared to intentionally head butt Mayweather in frustration as the two fought in Mayweather's corner.
"He did something dirty when it was his corner who said I was dirty," Mayweather said. "But I won the fight."
Mayweather later engaged in a verbal confrontation with HBO announcer Larry Merchant, calling him a name at one point and drawing a pointed response from the 80-year-old broadcaster, who said he would thrash the boxer if he "was 50 years younger."
While Ortiz claimed he was caught by a punch that came before Cortez ruled the fighters to continue, the referee said Mayweather did nothing wrong.
"Time was in, the fighter needed to keep his guard up. Mayweather did nothing illegal," Cortez said.
Mayweather, a 5-1 favourite in the fight against a champion 10 years younger, had vowed to go right after Ortiz and give the fans who bought the pay-per-view card at home an exciting fight. He mostly delivered on that promise, landing some good right hands in the early rounds and winning exchanges with his quickness.
Ringside punch stats reflected his dominance, showing Mayweather landing 73 of 208 punches to just 26 of 148 for Ortiz. Mayweather consistently beat Ortiz to the punch, and his experience and hand speed appeared to be the difference.
But he hadn't really hurt Ortiz and took some punches himself in the fourth round as Ortiz seemed to rally before the head butt touched off the series of events that brought the fight to an end. Ortiz quickly apologized to Mayweather after the head butt, giving him a hug and a kiss on the cheek while Cortez was busy taking a point away from him.
There was another quick hug in the centre of the ring as action was about to resume, followed by the 1-2 combination by Mayweather that put Ortiz on his rear. Ortiz tried to get up, but was still on his knees when the fight was waved to a close.
"There's two ways to look at it but as far as I was concerned I came here to entertain the fans and I think they were entertained," Ortiz said. "There was a miscommunication with the referee but nobody is perfect and this was a learning experience."
Mayweather made a minimum of US$25 million for his first fight in 16 months, a sum that will likely go up as the pay-per-view receipts are totalled. He could make even more against Manny Pacquiao next May should Pacquiao win his November fight with Juan Manuel Marquez and the two finally agree to fight.
Mayweather remained unbeaten in 42 fights, scoring the knockout he had predicted. Ortiz, who lost his 147-pound title, fell to 29-3-2.