The American has long vowed this would be his final fight, but even at the age of 40 and after almost two years of inactivity he showed few signs of decline in finally outclassing McGregor, who at the T-Mobile Arena was making his professional debut.
As had always appeared almost certain to be the case when interest in a match-up between the highest-profile figures from boxing and the UFC began building over a year ago, McGregor eventually proved levels below perhaps the finest fighter of the modern era.
He remained game and began with confidence, winning the first three rounds against all expectations, but as with Mayweather’s opponents in his other 49 fights, swiftly learnt his skills were inadequate as he became the first fighter to be stopped by him since Victor Ortiz in 2011.
Mayweather accepted that McGregor was better than he thought.
“He is a tough competitor and I thought we gave the fans what they wanted to see.
“He is a lot better than I thought he was, he used different angles and was a tough competitor but I was the better man tonight.
“Our game-plan was to take our time, let him shoot all his heavy shots early on and then take him down at the end, down the stretch.
“We know in the MMA he fights 25 minutes real hard and after that he starts to slow down.
“I guaranteed this fight wouldn’t go the distance. A win is a win.”
Mayweather’s victory takes his record to an unprecedented 50-0 and the 40-year-old insists this was his last outing in the ring: “This was my last fight tonight, my last fight, for sure. I chose the right dance partner to dance with.”
McGregor will walk away with his reputation intact after putting up an accomplished showing in his first professional bout.
The 29-year-old believes the referee Robert Byrd called time on the fight too early.
“I took the early rounds fairly handy,” he said. “I thought it was close, I thought the stoppage was a bit early, there was a lot on the line and I thought he should have let me carry on.
“I was just a little fatigued. He is composed and you have got to give it to him.
“I thought it was close. I get a little wobbly when I’m tired, it is fatigue, the referee could have let it keep going, let the man put me down. I am clear headed.
“Where were the final two rounds? Let me wobble to the corner and make him put me down.
“I’ve been strangled on live TV and came back. When you’re in here in the squared circle, everything is different.”
On the potential to get back in the square ring, the Irishman added: “We’ll see what happens. I am having a buzz, if anyone wants a knock give me a call.”
Savannah Marshall won on her professional boxing debut on the undercard when she earned a unanimous decision over Sydney LeBlanc.
The 26-year-old British super-middleweight, who was signed by Mayweather Promotions earlier this year, convinced with her jab throughout the course of the four-round fight to secure a 40-36, 40-36, 40-36 victory on the three judges’ scorecards.
America’s LeBlanc was hurt by a vicious jab early in the third round, but responded only with largely-ineffective aggression as Marshall repeatedly demonstrated the rounded abilities that once made her such a promising amateur.
“I felt brilliant,” the two-time Olympian said afterwards. “I’m really glad it was three-minute rounds because I prefer that over two-minute rounds.
“She was really tough like I knew she would be. I’m glad that I got out of there with a win against a top class opponent.”
Nathan Cleverly lost his WBA light-heavyweight title after being stopped in five rounds by Badou Jack.
The Welshman showed his bravery with his willingness to fight on while he was being outclassed but amid his inability to defend himself from increasing punishment, referee Tony Weeks came to his rescue.
Having previously considered retirement following the first defeat of his career, by Sergey Kovalev in 2013, he may again examine his future.
He eventually followed that defeat by an unsuccessful foray into the cruiserweight division, and also appeared fortunate to win his title when Juergen Braehmer was forced to withdraw through injury when they fought last year.
Such a one-sided defeat limits his options, and at 30 he lacks the ability to challenge the elite at 175lb that includes Kovalev, the great Andre Ward, and now new champion Jack.
“Jack was very strong,” said Cleverly. “He caught me and broke my nose. It was a downward spiral from there. I was wounded and protecting myself.
“I thought the stoppage was premature. He had just swung and missed but it’s up to the referee in the end. I’ll re-evaluate. I have a lot of miles left in me. I’m a two-time world champion. I have to take it from here and decide where I go.”