In Thursday's quarter-final, Swiss third seed Stan Wawrinka defeated a tearful Juan Martin del Potro, the 2009 champion, 7-6 (7/5), 4-6, 6-3, 6-2, to move into the semi-finals and face opponent Kei Nishikori.
"It was one of my toughest matches mentally and physically. Juan Martin's an incredible player," said Wawrinka.
Del Potro, the world number 142 and bidding to become the lowest ranked man to reach a Grand Slam semi-final in 16 years, was out to a 4-1 lead in the first set against Wawrinka.
The Swiss broke back in the seventh game and although Del Potro, whose career was almost derailed by a series of wrist injuries, saved two set points in the tiebreaker, a rare forehand error gave up the set.
The Argentine's bruising recent schedule had seen him claim an Olympic silver medal last month and he used that experience to claim the only break for a 4-3 lead in the second set.
But the Swiss was looking the fresher as the clock ticked towards and then past 1 a.m. He took the third set 6-3, hitting twice as many muscular winners.
Wawrinka, who had to save a match point in his third round clash with Dan Evans, will be playing in a third US Open semi-final in four years.
Del Potro was a spent force and gave up a double break in the fourth set on his way to defeat but leaving him at least with the compensation of being back in the top 65 after being ranked as low as 1,045 in February.
He was in tears on the eve of the final game before the two men embraced at the net.
"I can lose the match but I will never forget this. It's bigger than winning any match," said del Potro of the ovation he received.
"I'm so proud to get that from the crowd because I've been doing a big effort to play tennis again."