He now trails Roger Federer's record of 20 by six and is just three behind Rafael Nadal for second all-time.
Djokovic faced neither of his greatest rivals en route to the title in Flushing Meadows.
The U.S. Open final suddenly appeared to be slipping away from Novak Djokovic. He's healthy. He has a great team working with him. Victories that finished after 2 a.m. for 2014 champ Marin Cilic (against 19-year-old Alex de Minaur) and Nadal (against Dominic Thiem.) Nadal's retirement from his semifinal against del Potro because of an injured right knee.
And yet, after the events that unfolded in Saturday's women's final at Flushing Meadow, no one - not the players, the officials, administrators, the fans or the sport itself - emerged as a victor.
"I was so close to the desired level, and then I completely underplayed that match".
Angelique Kerber went from No. 4 to No. 3.
All that frustration was washed away when he struck the overhead victor to clinch victory over Del Potro, Djokovic falling to his back, arms and legs spread savouring the moment.
Also marking a career-best ranking Monday is Caroline Garcia, who rose to No. 4, the highest for a woman from France since Amelie Mauresmo held that same spot in June 2007. The most common utterance from chair umpire Alison Hughes aside from the score was undoubtedly, "Quiet please, players are ready", as she tried to stifle the rowdy spectators so del Potro and Djokovic could serve.
But Del Potro needed more than just goodwill to beat Djokovic at his best, he needed his mighty forehand to be flawless and the rest of his game to back it up.
6-3 victory under the roof at Arthur Ashe stadium - it was raining in NY - pulled him level with Pete Sampras for third on the all-time men's list. 'I thought of tennis, thought of the emotion that tennis provokes in me.
"Novak is too fast".
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 the roof is closed, trust me, it's very, very loud down there".
Djokovic's coach, Marian Vajda, called that moment the match's "turning point, obviously".
That proved to be the key moment in the match. He had the upper hand in the second set tie-breaker but couldn't convert, and after fighting back from a break down in the third set he served up a double fault to give Djokovic a chance for the final break of serve.
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.
Trying to force the issue, he hammered a backhand wide and Djokovic broke before serving out for victory. Later, after winning a point, Djokovic put that finger to his ear, as if to say, "Who are you cheering for now?!"
"I got here to the final after nine years which is incredible because this is my favourite tournament on tour".
It was Djokovic's 15th win over the Argentine and fifth in five at the Slams.
Djokovic won with his customary elastic defence, and regular forays to the net.
And then came Sunday's pivotal game, a 20-minute, 22-point epic.
This time a year ago Djokovic was injured and uncertain about his future direction.
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.