He closed his win with a yelp, barely audible over del Potro's ebullient fans. But even the straight-sets win had its moments, moments of vintage Djokovic: an on-the-line victor, an overhead smash, a passing shot, a backhand cracker.
Djokovic now joins Pete Sampras in third place on the all-time list of Grand Slam titles, trailing only Roger Federer (20) and Rafael Nadal (17).
The story of the weekend, however, from the tournament was on the women's side, as there was a little bit of drama in the championship match between Serena Williams and Naomi Osaka.
Del Potro was looking at having to become the first man since Pancho Gonzales in 1949 to win the USA title from two sets down.
"There was always part of me that imagined and believed and hoped that I can get back (to) the desired level of tennis very soon", said Djokovic, whose operation was in February.
Top-seeded Nadal had been favored to win this tournament from the start.
Del Potro went into Sunday's final buoyed by seeing off defending champion and world number one Nadal who was forced to quit their semi-final with injury.
Amid increasing noise between points and serves, which prompted frequent interventions from chair umpire Alison Hughes, the previously assured Djokovic - who missed the tournament past year due to an elbow injury - appeared agitated.
Djokovic has only ever lost one match from more than 200 when he has led by two sets - to Austria's Jurgen Melzer at the 2010 French Open - but there was no sign of that happening again.
"We also think the issue of coaching needs to be addressed and should be allowed across the sport", Simon said.
"I've been during all my career learning with Novak, Roger, Rafa, seeing them winning these events very often".
"I can not lie there were a lot of moments where I was doubtful, where I didn't know if I would be able to play at the highest level, compete for Grand Slams with these guys".
"I'm just doing my job, trying to be an example for the kids, to teach them that you have to do effort to get your goals in your life", del Potro said.
The Argentine put his admiration aside Sunday and made it hard for Djokovic to gain an edge, despite the score of the first set.
Djokovic won a tiebreaker to take the 95-minute second set. The atmosphere had finally got to him as he dropped three consecutive games after not facing a single break point in the first set.
Before the final, Del Potro had seen 41% of his serves unreturned in the tournament.
Eventually, the Serb held.
After Mohamed Lahyani's mid-match pep talk to Nick Kyrgios caused uproar, Carlos Ramos became the third player in the women's final.
But against one of the best returners in the business, Del Potro needed to be far more assertive. He had all but deflated.
Responding to the chants from the crowd for Del Potro, Djokovic said, "This might sound amusing, but my nickname is Nole". Off court, it was a story of two comeback kids. One man with no excuses is three-time masters champion Alexander Zverev who remarkably has only gone beyond the fourth round of the Grand Slams only once at this year's French Open. He has had four wrist operations since then. "I really am", he said. The only higher overnight rating, a 2.7, was a prime-time 2015 window of quarterfinal action that included Serena playing her sister Venus and Novak Djokovic vs. Feliciano Lopez. His eyes were still red when he spoke to reporters later.
"I owe it to them".