Djokovic was thrilled to match Pete Sampras with a 14th Grand Slam title, but he said it's Federer and Nadal who have made him the player he is.
Del Potro, who was very emotional at the end of the final - his first since he won at Flushing Meadows back in 2009 - gushed over his opponent in a moving speech.
Del Potro - the third seed - had earlier lauded Djokovic, telling ESPN: "So happy to play in the final against this magnificent idol".
With all the singing and noise levels inside the stadium, it felt to Djokovic like he was at a football match but he thanked the fans of both sides for creating such an unbelievable atmosphere. I had to disconnect a little bit. "They deserve to win". I really am, ' Djokovic said.
Del Potro had a 3-1 lead in the tiebreaker before Djokovic recovered to take it. And it all started with Djokovic getting erked by crowd reaction and constant singing for Del Potro.
'I have utmost respect for what they have achieved on the court, but also the champions, role models they are off the court.
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Ashleigh Barty and CoCo Vandeweghe have won the U.S. Open women's doubles final, beating Timea Babos and Kristina Mladenovic 3-6, 7-6, 7-6 at Arthur Ashe Stadium.
The Serbian fans were not behind.
Djokovic is trying for a third U.S. Open title and 14th major overall, which would tie Pete Sampras for third place on the career list.
Djokovic said it was the kind of heavyweight clash he's learned to embrace.
Having struggled earlier in the year, Djokovic put injury behind him and found the form that saw him become one of the game's greatest in recent years.
"I am still here because I love what I am doing".
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"I really felt for Serena. I tried to take the best out of myself in those moments and get myself in this position".
This was Djokovic's third championship in NY, along with those in 2011 and 2015, as he drew even with Pete Sampras on 14 major to be third all time - trailing only Roger Federer (20) and Rafael Nadal (17).
Djokovic expressed his love for Sampras and said he was hoping to see him at Flushing Meadows on Sunday.
The tension and fireworks of the Osaka-Williams clash were left behind during a relatively calm and composed baseline battle between two friends and familiar foes who had played each other 18 times, with Djokovic holding a commanding 14-4 edge. Since then, he's missed extensive time with injuries to both wrists. Barty and Vandeweghe kissed the trophy and won $700,000 for their championship.
Former world number one Djokovic equalled Pete Sampras' haul of 14 slams after outlasting Del Potro 6-3 7-6 (7-4) 6-3 to lift the trophy for a third time in NY.
It is Djokovic's thid U.S. Open title and first since 2015.
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With the Arthur Ashe Stadium roof closed as heavy rain swept NY, conditions were slow and sluggish.