Osaka's winning the championship also must have given impetus to other Japanese tennis players, including Kei Nishikori, who finished second in the 2014 U.S. Open.
Del Potro hailed the victor after losing in his first final since winning the Wimbledon Title in 2009.
While del Potro fought back in the third set and even broke back, Djokovic was able to get the deciding break at 4-3 and was able to hold the final service game to win the match.
There was a time when Pete Sampras's tally of 14 Grand Slam singles titles - the last of which came at the U.S. Open in 2002 - seemed like the acme of sporting achievement in men's tennis. He finished with a flourish, taking the last three games.
This is Djokovic's second straight Grand Slam singles title this season following Wimbledon 2018 and a 14th overall to tie American Pete Sampras for third all-time.
The resurgent 31-year-old is now just three slams behind Rafael Nadal and six slams back from Federer.
The Serb, who was back in the final for an eighth time and contesting his 23rd Grand Slam final - the third most in men's tennis history - was serving exceptionally well and earned a break in the eighth game after showing tremendous patience before successfully serving out the set. Djokovic, victor of the 2011 and 2015 Opens and a former No. 1, is on a rollicking roll in recent months, including July's Wimbledon title, since having elbow surgery in February.
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'I don't know the answer.
The Serb now leads del Potro 15-4 in career meetings, and 5-0 in Grand Slam encounters.
"I was so close to desired level, and then I just completely underplayed that match". He eventually succumbed to the mounting pressure in the third game as Djokovic looked to take over proceedings. Her grandfather, who lives in Nemuro, Hokkaido, expressed his joy, saying, "I want her to make a spectacular showing at the 2020 Tokyo Olympics, too".
Djokovic had elbow surgery in February to finally fix a problem that had dogged him for more than a year and found his best form again this summer. Del Potro would not rue how many of those could have been his had he been injury-free all those years.
When it ended, thanks to a three-game closing run by Djokovic, he flung his racket away and landed on his back, arms and legs spread wide.
The tiebreaker was resolved thanks to more del Potro miscues on his forehand side, as he looked more and more tired.
Leading 4-3, Djokovic caught Del Potro off guard with his exceptional patience and strong strokes to break Del Potro's serve.
The three-time US Open victor said his hike in France had given him a fresh perspective on life. "Of course I'm sad because I lose but I'm happy for Novak, you deserved to win".