It was a cruel fate for Nadal who beat Kevin Anderson in the final a year ago and was aiming for his 18th major title. But that degree of wastefulness could be punished by del Potro. He endured multiple wrist operations after he won the Open in 2009, but he is finally getting back to his form of almost a decade ago.
The 2014 US Open finalist changed tactics in the second set and won 14 of his 15 net points.
Djokovic and Argentine Del Potro, who advanced when Rafael Nadal retired injured from their semi-final, meet in the final on Sunday at 21:00 BST.
On that day it was his right knee, the same one that needed attending to on Friday night and in the semi-final against Del Potro. And while he still had the devastating forehand that's been one of tennis' signature shots and carried him to the 2009 title, repeated wrist injuries had made him one dimensional on the backhand side.
He said: "It could be another big battle, as the Wimbledon match was".
"He treats others the way he wants others to treat him", Djokovic said of the respect Del Potro commands in the locker room. Then I think it was a little bit better.
"I didn't know if I will be a tennis player again or not. Reaching finals, winning titles, having my highest ranking ever in this moment, everything is nearly ideal", del Potro said, smiling.
A nasty ankle roll late in the first set had fans fearing Nishikori mighty be forced out of his semi.
When he swept to the 2009 title in NY, he was just 20 years old and expected to establish himself as a permanent rival to Djokovic, Federer and Nadal.
The world number one had headed into the tie after a marathon quarter-final tie against Dominic Thiem, who pushed the Spaniard to the limits on a humid night in NY.
"When I saw him with bad movements [in the second set], I start to play aggressive, putting him running a lot".
Thiem fought hard to win the fourth set.
Yeah, I waited as much as I can. When you play tournaments like this, when you have a day off during matches, it's very important to put your body in rest and do the treatments in the good way.
He said: "Well, I personally like him very much, not just as a player but as a person".
Back from career-threatening wrist problems, Del Potro has shone throughout this tournament, but will have his work cut out to deny former world No. 1 Djokovic if the Serbian reproduces the form he showed on Friday. Thousands in the crowd would lend their voices to the song; yet others would try to drown them out with support for Nadal. After holding their serves for three games each, del Potro broke Nadal's serve to inch ahead at 5-4, with Nadal levelling the score again in the next game. I'm happy for that'.
"Well, you see the friends who came to watch me?"
"It means a lot to be back in the final", added Del Potro after his sixth win over Nadal, all on hard court. "Even before I went through the whole process of surgery, post-surgery recovery, I was still feeling for players that went through injuries", Djokovic said.