Djokovic and del Potro have squared off 18 times but never in a major final.
Del Potro was playing in his first Grand Slam singles title since he won the 2009 U.S. Open as a 20-year-old.
After winning the first set 6-3, Djokovic was leading 3-2 in the second set (having broken Del Potro) and was serving to extend his lead to 4-2. 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. "Ole Ole Ole. Delpo, Delpo" reverberated around the stadium in support of Del Potro.
Djokovic and Del Potro walked on Arthur Ashe Stadium court with the Billie Jean King National Tennis Center still buzzing over the controversial women's final on Saturday, won by Japan's Naomi Osaka after Serena Williams incurred three code violations.
Thankfully, Del Potro's injury woes look to be behind him.
In the immediate aftermath of Djokovic's victory, he embraced del Potro at the net in a heartwarming show of class and respect between the friends and foes.
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Novak Djokovic celebrates with the trophy after winning the 2018 US Open title.
Amid increasing noise between points and serves, which prompted frequent interventions from chair umpire Alison Hughes, the previously assured Djokovic - who missed the tournament previous year due to an elbow injury - appeared agitated.
"I want to say Pete, I love you, you're my idol", said Djokovic of Sampras.
"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. He made one last stand by breaking and holding for 3-all.
"To support of my loved ones, my kids, my wife, my team of people that has been there with me through hard times as well".
"Difficult times but you learn from adversity. when you have doubtful moments when things are not working out as you want (them) to and I try to take the best out of myself in those moments and thrive on the love and support I receive from my closed ones and get myself in this position", Djokovic expressed. During the time in-between, he had four wrist surgeries, including three on his left wrist, and contemplated quitting the sport altogether. "I really wish him all the best and I know he's going to stand here again with the champions trophy".
This was Djokovic's third championship in NY, along with those in 2011 and 2015.