In the 10 minutes that followed her stunning 6-2 6-4 victory against the most dominant female player of the past two decades, as Arthur Ashe Stadium was being prepared for what would be a deeply awkward trophy ceremony, Osaka sat all alone in her chair as parts of the 23,000-strong crowd booed loudly.
Djokovic tied Pete Sampras for third place on the all-time Grand Slam list with 14.
Djokovic has won 13 of his 14 Grand Slam titles since 2010, when the prize money for the champion moved past the £1m mark at all four majors.
Del Potro was the sentimental favourite as he attempted to win a second slam title nine years after his first, having suffered two serious wrist injuries, the second of which he feared would end his career.
Djokovic broke del Potro early in the set to take a commanding position, but del Potro later broke him back and looked on the verge of taking full control of the match's momentum.
A focused Djokovic continued to apply pressure in the third set until Del Potro finally cracked on serve to fall behind 5-3, with the Serb closing out the match with a ferocious overhead victor. That Williams lost a point, then a game, and was fined $17,000 are what will be remembered about that final. At 1-1 in the second set, Djokovic suffocated Del Potro from the baseline to force out errors from the big man and got an early break.
Djokovic particularly struggles in the hot and humid conditions that hit NY over much of the fortnight and looked out of sorts against Marton Fucsovics in the first round - splitting the first two sets, he trailed 4-2 in the third - Joao Sousa in the fourth and giant killer John Millman in the quarterfinals.
Early in the tournament the extreme heat and humid conditions in NY were clearly troubling Djokovic.
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After the controversy surrounding Serena Williams' defeat by Naomi Osaka in Saturday's women's final, a high-quality match between two of the top male players ensured tennis was once again the talking point.
"I was playing nearly at the limit, all the time, looking for winners with my forehands, backhands, and I couldn't make it", del Potro said, "because Novak (was) there every time". And now she's the first player from Japan to win one.
In the post-match ceremony, Osaka said to Serena: "I'm really grateful I was able to play with you".
Djokovic collects $3.8 million and his third U.S. Open championship.
"Today I really am".
Djokovic captured the first of his 12 majors in Melbourne in 2008, but it was three years before he added his second.
"When I had my surgery I could truly understand what Juan Martin was going through", Djokovic said after the win.
The 13th-seeded team of Barty and Vandeweghe knocked of the No. 3 and No. 1 seeded teams en route to their first Grand Slam doubles title as a team. In terms of results, I played the finals of Queen's, won Wimbledon, won Cincinnati, and won US Open.