Djokovic reached the final at Flushing Meadows after breezing past Kei Nishikori in the last four, beating the Japanese star 6-3, 6-4, 6-2.
It’s the eighth time the Serb will have been in the final in New York, though he has only lifted the trophy twice before.
He will meet 2009 champion Del Potro on Sunday after Rafael Nadal retired after two sets during his semi-final with the Argentine.
Djokovic is on the hunt for his 14th Grand Slam title, which would draw him level with American legend Pete Sampras.
And he’s warned that he’s always looking for ways to improve.
“As thousands of other tennis players around the world, I’m trying to be the best I can be,” Djokovic said immediately after beating Nishikori.
“I’m working hard every day, as hard as anyone else, and obviously I’m trying to reach certain heights that I visualise.
“Every time I achieve something big I feel there is a new mountain peak to conquer. I don’t see any limits or an end around the corner.”
Djokovic and Del Potro have faced each other 18 times before with the Serb leading the head-to-head 14-4.
Indeed, Djokovic has won the previous three meetings with Del Potro’s last win coming at the 2016 Rio Olympics.
The pair have met twice before at the US Open with Djokovic winning in straight sets in both 2007 and 2012.
But this is the first time the two will have clashed in a major final with their last final meeting coming at the Shanghai Masters back in 2013.
“We’ve never faced each other in a Grand Slam final so that will be something new for both of us,” Djokovic said.
“But we’ve played 18 times against each other. I have tremendous expect for him.
“He’s a big match player and I’m sure the final will be a thrilling match.”
But Del Potro is under no illusions as to who the favourite is.
“Well, it will be a difficult match because we are close friends,” he said.
“For sure we both want to win. But Novak has won Wimbledon already.
“He’s playing so good. He will be the favourite to win on Sunday.”