Dominic Thiem, which lasted five sets and almost five hours.
The No. 1-seeded Nadal has a history of tendinitis in his knees and he said he felt a problem in the right one early in the first set.
Over and out: Rafael Nadal, of Spain, waves to fans after retiring from the match.
"That was not a tennis match at the end, no? It was one tennis player playing, the other standing at the side of the court".
The three-time champion retired at the end of the second set with Del Potro leading 7-6 (7-3) 6-2 on Arthur Ashe.
Where can I stream Rafael Nadal vs Juan Martin del Potro? .
Novak Djokovic of Serbia celebrates victory following his men's singles semi-final match against Kei Nishikori of Japan on Day Twelve of the 2018 U.S Open on September 7, 2018 in New York City. I didn't expect to get in another grand slam final. "You could imagine very hard for me to say good-bye before the match finish".
Grimacing with every sudden move, the 17-time Grand Slam victor called for the trainer during the changeover on serve at 2-1 in the second.
The popular Argentinian, whose career has been blighted by serious wrist problems since that maiden grand slam success, will face Novak Djokovic or Kei Nishikori in the final.
Nishikori began the third set with a confident hold of serve but the 28-year-old made four unforced errors in his next service game to set Djokovic on the road to victory.
Thankfully, the 21st seed appeared to avoid injury and duly played his best tennis of the match after dropping the first set, fighting hard to stay with his illustrious opponent.
Nadal tried to play through the pain but when Del Potro blasted a forehand victor to go ahead 7-6 (3) 6-2 the Spaniard removed his headband and said he could not continue.
This one, given the added difficulty created by unusually high heat and humidity, would certainly be meaningful.
Djokovic missed the tournament past year because of an injured right elbow that eventually required surgery. "I still here. I still here because I love what I am doing", said Nadal.
One of the greatest players of all time, the one chink in the Spaniard's armour has always been his knees with injuries plaguing him throughout his career.
"I had my biggest memories on this court in 2009 when I beat Rafa and Roger (Federer, in the final)".
Nadal, who reached the last four in NY on the back of brilliant shot-making and incredible movement, looked out of sorts early against Del Potro and struggled to cover the court with his usual tenacity.