"When I had surgery on my elbow earlier this year I could truly understand what Juan Martin was going through with his surgeries during the two or three years that kept him away from the tour", said Djokovic.
Del Potro was looking at having to become the first man since Pancho Gonales in 1949 to win the United States title from two sets down.
This new trophy is a tribute to Novak Djokovic's awesome consistency at this event over the years.
Del Potro has a fervent support at the US Open and was backed by a noisy support as thousands of Argentine fans descended on the Arthur Ashe Stadium wearing their national colours of light blue and white.
When asked if the 31-year old Serbian could break Federer's record, Del Potro sounded quite confident as he said, "Of course he can". It was a contest not without its chances.
Between them, Federer, Nadal and Djokovic have won 47 of the last 55 slam titles, but Del Potro has no regrets, saying: "It is a big challenge to take these kind of tournaments from them". He was soon 3-1 up in the second set before Potro carved out his first break point of the match to level at 3-3.
"To be honest, I was crying till now", Del Potro said at a news conference.
She said: "For me, Novak, the only difference is sometimes mentally he checks out". But Novak deserved to take the trophy. Barty and Vandeweghe won the second set tiebreaker 7-2 and won the third 8-6 to win for the second time in four meetings this season against Babos and Mladenovic.
"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". He's a great champion.
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The triumph for the sixth seed saw him complete the Wimbledon-US Open double for a third time and he remains only the eighth player to have achieved the feat in a calendar year.
The victory will also see Djokovic rise to No.3 in the world behind Nadal and Federer - the rankings again reflecting the "Big Three" status they have shared for so long.
But since then, his career hasn't quite rocketed up because of his concerns with wrist injuries where he has had four surgeries so far. And able to build momentum once more, the results have showed in 2018.
"I was so happy to be playing the final against this magnificent idol", added Del Potro of his close friend Djokovic. "I feel good with my two-handed backhands, as well". I think that was one of the most important, so to say, moments and periods of my life, my tennis career, my development.
"I know people always like to compare any top player's game or performance with some previous season where he was dominating and they've done that with me".
"I breathed in the new inspiration, new motivation. I can't believe she managed to get all the way up", Djokovic said.
Despite defeat, world number three Del Potro remained proud after an achievement he never thought would have been possible during his injury hell. It was futile now.
While Streep was beside herself, Jerry Seinfeld had more of a skeptical look. "I owe it to them".
Djokovic has been successful in five of the last six Grand Slam finals he's played dating back to Wimbledon in 2015. I just felt like I had a new breath for this sport.