Mayweather, 41, a former five-division world champion, floored Nasukawa three times before the end of the first round. Nasukawa's corner threw in the towel after the third knockdown, and the 20-year-old was left in tears after being humbled by the retired Mayweather.
Nasukawa was twice dropped with precise left hooks before a short right hand put him down for a third time.
After his quick win, Mayweather insisted it did not change the fact that he is retired.
"It was all about entertainment. We had fun," Mayweather said. "I'm still retired. I don't look forward to coming back to boxing. I did it just to entertain fans in Japan. I'm still retired, I'm still 50-0, and Nasukawa is still undefeated and a hell of a fighter."
Mayweather's comments pretty much killed talk of him being interested in fighting the winner of the Jan. 19 bout between Manny Pacquiao, whom Mayweather outpointed in May 2015, and Adrien Broner.
Mayweather looked sharp despite being in retirement after stopping the UFC's Conor McGregor in his last professional boxing match 16 months ago.
Since this was an exhibition bout, with no official judges, the fight will not go on Mayweather's professional boxing record. However, the fight was still worth $9 million to Mayweather, according to what he disclosed on social media recently.
There were doubts Mayweather would turn up for the event against a kickboxer less than half his age at Saitama Super Arena, north of Tokyo, for an event organized by Rizin, the largest MMA promoter in Japan.
Mayweather, who lives in Las Vegas, distanced himself from the promotion in November but turned up for the boxing-rules contest that was the last of 14 bouts.
A delay of over two hours did not help ease fears that Mayweather was not going to show. When he finally did, there were protracted preliminaries before less than three minutes of action.
Nasukawa entered the ring with a 28-0 kickboxing record and 4-0 MMA record. The bleach-blond kickboxer, who made his professional debut at age 16, said before the fight: "I want to be the man who changes history. I'll do that with these fists, with one punch -- just watch."
But Nasukawa never landed a meaningful punch.
Mayweather began smiling and relaxed. When he decided to throw punches, it was not long before the first left hook landed on Nasukawa's temple. The Japanese fighter stumbled to his feet and tried to get his jab working, in a desperate attempt to stop Mayweather's forward march.
But Mayweather's laser-like accuracy saw another left hook find the target. When Nasukawa began throwing more punches after getting up from the second knockdown, Mayweather caught him with a short right, and the home hero's corner decided enough was enough.
Boxers have faced MMA fighters before. Mayweather, who first retired in September 2015, stopped Ireland's McGregor in the 10th round in August 2017, and Muhammad Ali fought Japanese wrestler Antonio Inoki in a 15-round draw in 1976.