McGregor delivered a crisp uppercut in round one and, though he edged close to breaking rules with several punches to the back of the head, he imposed himself admirably without ever looking as though he would knock out Mayweather.
The American, who came out of retirement for a potential $300m (£230m) pay day, executed a gameplan which pounced on McGregor’s lack of conditioning for the late rounds which prove so key on big fight nights.
As the Irishman tired, Mayweather upped his ferocity and by round nine the 40-year-old began to stalk his opponent, whose legs were weakening under more successful shots.
And in the 10th, with McGregor again near the ropes and offering little, the fight – which followed weeks of manic build-up, spiteful words and chaos – was over.
Referee Robert Byrd’s stoppage may have arrived too early for some, as McGregor’s early effort meant he was in the contest on the scorecards.
But the 29-year-old was wilting. His effort and display should be commended, but Mayweather’s poise and invincibility remains constant into retirement.
Was the hype justified?
Those who watched this bout can say they witnessed history, with Mayweather’s victory taking him past the late Rocky Marciano’s perfect 49-fight record.
And this may yet be the richest fight in history, surpassing the reported $620m (£480m) earned by Mayweather’s win over Manny Pacquiao in 2015.
The presence of A-list celebrities such as Bruce Willis and Jennifer Lopez underlined the high-rolling nature of a bout engulfed in chaos.
But those who saw it simply as a garish race for dollar bills wanted to see the circus justified.
US news networks set up studios on Las Vegas’ strip, with debate on the legitimacy of the fight dominating the build-up.
MMA guests said boxing was dated, and were accused of speaking with an ignorance towards the sweet science. One pundit said Mayweather would look like Michelangelo against a man whose boxing style would be “paint by numbers”.
Elsewhere, local airports adopted emergency measures to deal with an influx of high rollers, while sportsbooks on the city’s famous strip were braced for record stakes.
But could the hype be justified? Was Mayweather too old? Would McGregor’s relentless undermining of his rival work?
No, no and no. Critics of the contest will likely point to the ease with which Mayweather upped the ante as evidence this was always a mismatch.
He remains at his best when in the spotlight, delivering when booed, winning with breathing space.
The fact he had already fought 39 times by the time McGregor quit a plumbing apprenticeship to focus on MMA underlined the gulf in experience.
It showed, though ‘The Notorious’ has captured the imagination of new fans and will be considerably richer – both financially, and in ring craft – for taking on such a challenge.
He boxed, well at times. But, like Hall of Fame boxers who tried before him, he did not have enough to shock Mayweather.
How did the fight play out?
After the frenetic build-up, the talking stopped before both men stepped into the ring – and McGregor glared at his rival with intensity before the bell.
In round one, he landed a crisp left uppercut and later posed with his hands behind his back. He seemed to consciously exaggerate his movement at times, lending substance to suggestions from pundits his MMA footwork would by a key part of his weaponry.
But a stiff right from Mayweather in the second drew screams from the masses, and ‘Money’ smiled cheekily at the TV cameras when on his stool between rounds.
Was he toying with his man? There were moments it appeared so. He began to walk forward more in the fourth but felt a solid left counter.
Chants of “ole” provided backing for the underdog, who angered Mayweather with persistent punching to the back of his head.
The American’s response was a shove in the chest after the bell in round five as he became notably more spiteful.
His punches began to look loaded, but it remained close. McGregor’s early punch volume won rounds, Mayweather’s progress through the gears, albeit slow, closed the deficit by the seventh, when he jolted his foe with a counter right.
The ninth round would take the boxing novice past the 25 minutes he faces in a UFC bout, and fatigue became undeniable. He swayed, at times a sitting duck to be picked off as Mayweather landed, notably with a slappy left hand.
And then came the 10th. McGregor screamed when the stoppage came, as if to intimate he had more left. He probably did, but barring him finding power we had not yet seen, he was done. Byrd brought the inevitable forward.
And with that, Mayweather returned to retirement with his perfect record in tact.
What next for McGregor? His spirit and magnetism is such that he will continue to break down barriers.
He deserves immense credit, but Mayweather’s standing in boxing history remains unblemished.