Victory takes the battling Serb level with American great Pete Sampras’ mark of 14 Grand Slams.
Djokovic, playing in his eighth final in New York and already the champion in 2011 and 2015, is now just three Slams behind Rafael Nadal and six back from the all-time record 20 held by Roger Federer.
It was also the third time the 31-year-old Serb – who missed last year’s tournament with an elbow injury which sent his career into a mini-crisis – completed the Wimbledon-US Open double.
“I want to say Pete, I love you, you’re my idol,” said Djokovic of Sampras.
“To the support of the loved ones, my kids, my wife, my small team of people that has been there with me through difficult times as well,” added the Serb who underwent elbow surgery after the Australian Open in January.
Argentine Del Potro backed Djokovic to surpass Federer’s mark of 20 Slams.
“Of course he can. Novak has everything to make records in this sport,” said the Argentine.
“I was so happy to be playing the final against this magnificent idol,” added Del Potro of his close friend Djokovic.
“He knows that he’s one of my friends on tour and he knows he’s one player I want to watch win on tour. Of course I’m sad to lose but I’m happy for Novak as well. You deserve to win.”
The result also means that 50 of the last 55 majors have been won by the ‘Big Four’ of Federer, Nadal, Djokovic and Andy Murray.