McGregor, making his professional boxing debut, had boasted he would knock out the 40-year-old American early but his lack of ring savvy betrayed him as Mayweather improved to 50-0 to surpass heavyweight great Rocky Marciano's 49-0 record for most wins without a loss or draw.
"He (McGregor) is a tough competitor and I think we gave the fans what they wanted to see. I owed them for the Pacquiao fight," Mayweather said post-fight.
"Our game plan was to take our time, let him shoot his heavy shots early and take him down at the end.
"We know that in the MMA he fights 25 minutes real hard. After 25 minutes (tonight) he started to slow down.
Whether the megafight will be the richest of all-time, as promoters predicted, is still to be determined but Mayweather left no doubt of his place in the pantheon of boxing greats in what he said was his last fight.
By the fourth round Mayweather went on the attack and started landing blow after blow against a suddenly desperate McGregor who was bravely hanging on while clutching and grabbing the American.
In the 10th, Mayweather moved in for kill pinning a visibly fatigued McGregor against the ropes and landing a flurry of punches when the referee stepped in to stop the fight.