Djokovic, patient and strong through two punishing weeks, became a three-time U.S. Open victor and 14-time Grand Slam champion with his 6-3, 7-6 (4) 6-3 victory over del Potro under the roof at Arthur Ashe Stadium.
"Of course he can", said Del Potro when asked if Djokovic can claim the record over Federer who is nearly six years his senior.
He now trails Roger Federer's record of 20 by six and is just three behind Rafael Nadal for second all-time.
He missed last year´s tournament with an elbow injury which sent his career into a mini-crisis.
Juan Martín del Potro is in search of his second US Open title. "When they shout "Ole, ole, ole, ole", that's what I hear", he said of the raucous chants for Del Potro.
But off the back of a 24-shot rally, Djokovic broke again for 5-3 and he was within tantalising touching distance of his 14th Grand Slam title, just three months after he had left Roland Garros in despair after a shattering quarter-final exit.
Djokovic was soon 3-1 up in the second set before Del Potro carved out his first break point of the match to level at 3-3.More news: Astronauts on International Space Station showcase power of Hurricane Florence in photos
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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).
When another forehand error cost Del Potro his serve early in the second, all the momentum was with Djokovic. Now he has backed that up at the US Open, marking the fourth time in his career that he has won multiple majors in a season.
But instead of that victory proving a launchpad for a sustained challenge at the Grand Slams, Del Potro battled wrist injuries which required four surgeries.
Playing at a career high three in the world, Del Potro insists he is happy to be playing in the era of Djokovic, Federer and Nadal.
He picked up the pace with straight-sets victories over France's Richard Gasquet, Portugal's Joao Sousa, Millman and 2014 finalist Kei Nishikori to arrive at a title tilt with good friend Del Potro.
"You learn from adversity ... when you have doubtful moments when things are not working out as you want (them) to".
Del Potro, 29, won the only Grand Slam title of his career by upsetting Federer in NY in 2009, but couldn't swing the upset Sunday. "I think that's why people love him".
Since bursting out of the slump with an unexpected Wimbledon title he has gone from strength to strength, adding a long-awaited Cincinnati Masters title to his resume before adding the US Open title to those he won in 2011 and 2015.