The defending champion needed almost five hours to defeat ninth seed Dominic Thiem in a deciding tie-break after losing the opening set 6-0 and will face Juan Martin del Potro on Friday in a rematch of last year's semi-final.
It was the second time someone had taken a set 6-0 against Nadal at the US Open, with Andy Roddick doing so en route to a straight sets win in 2004. Thiem was also 5-3 ahead in the third set and 4-2 in the fourth before he was reeled in by Nadal, the three-time champion in NY.
This is a rematch of the French Open final, won by Nadal in June.
The two players met in the semis at last year's U.S. Open, a match Nadal won in four sets. "He will have his chances in the future without a doubt", Nadal said. "For me it was a tough start".
"I would say the first really epic match that I played".
Thiem - with his girlfriend and fellow tennis player Kristina Mladenovic watching from the stands where Hollywood star Ben Stiller was also present - played well, however, Nadal was just too good as he executed the third of three set points on his opponent's serve to claim the momentum.
True to form, the defending champion improved significantly in the second set and things went with serve until game eight as Nadal broke for a 5-3 advantage.
He said: "I have my trophy at home. But in few days I will look back and will remember how great it was to play in front of a packed Arthur Ashe - this great match".
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"Tennis is sometimes cruel, this game didn't deserve a loser but there has to be one and, if we skip the first set, we were well matched from start to finish", he noted.
Asked about that at his news conference, Thiem said with a chuckle: "Well, I don't think he's really sorry".
It took a while for Nadal to figure out what was wrong and become Thiem's equal in entertaining, body-punishing baseline exchanges that inspired loud gasps from spectators. "He is young and has plenty of time to win tournaments".
Thiem was broken serving for the set and then could not hold on for the tie-break, saving two set points but not a third after planting a volley wide with the whole of the court available.
Perhaps Thiem, after a change of socks and shoes, looked the fresher going into the decider but he needed to save two break points at 2-2, one with an ace, to maintain parity.
"(I am) sad for him because when [he arrived at] this moment, he did all the things well to win the match.
He'll face 2009 champion Juan Martin del Potro next.
Get 3 months free Sport HD + Entertainment on a 12 month plan and watch the US Open and ATP World Tour on FOX SPORTS. I had the passion to keep going always'. Del Potro, who has been the most dominant men's player this year, will have to go full throttle if he has to release Nadal's stranglehold over him.