The fight was stopped in the 10th round by the referee as the American landed punches at will and the Irishman's stern resistance came to an end.
McGregor showed he is more than just a big mouth, keeping Mayweather interested for the first half of the fight, before his stamina began to fade.
Mayweather may lack the tremendous power of some fighters in the super welterweight division, but his lighting speed and near-flawless technique allowed him to pepper McGregor's head with a barrage of punches which increased in frequency as the fight went on.
The Irishman, who began the fight full of pep and purpose, was little more than a lumbering target by the 10th round, when referee Robert Byrd correctly stopped the fight.
With many expecting the fight to fizzle after such a hype-filled build-up, McGregor at least proved he had learned a lot in his boxing crash course over the past few months.
The 29-year-old was the more aggressive boxer in the opening rounds, but he did not launch himself at Mayweather in the hope of landing a lucky haymaker, as many predicted he would.
The Irish southpaw came at his 40-year-old opponent in the early rounds, using his extra reach to extend his right mitt as a probe, before firing flurries of punches. Mayweather defending himself easily, but he was at least unable to land any meaningful hits of his own.
