The world's top two men have comfortably been the best players at the tournament with Djokovic dropping just one set in five rounds and Nadal not having been broken.
While they have reigned supreme, defending champion Andy Murray slumped to a quarter-final loss to Stanislas Wawrinka and five-time champion Roger Federer was gone by the fourth round.
On Saturday, six-time major champion Djokovic, playing in a 14th successive Grand Slam semi-final and seventh in a row in New York, where he was a 2011 winner, will attempt to make Wawrinka's maiden last-four appearance a painful experience.
Nadal, the 12-time Grand Slam title winner and the 2010 New York champion, faces Richard Gasquet, the French eighth seed and one of his closest friends on tour.
Gasquet, like Wawrinka, has reached his first semi-final of the US Open. The two outsiders also have something else in common -- a lethal expertise in the one-handed backhand, something that neither Djokovic nor Nadal employ.
"I'm quite happy with my backhand. That's one of my best shots," said Wawrinka, who for the first time in his career has gone deeper into a Grand Slam than his more-celebrated compatriot Federer.
"I changed when I was 11 because my two hand backhand was not good enough."
Wawrinka, who has made the semi-finals for the first time at a major at the 35th attempt, will need that weapon on Saturday as Djokovic, who has already won the Australian Open this year, enjoys a 12-2 career lead over the Swiss.
Wawrinka's last win was in 2006 and he was forced to retire through illness when the pair met in the fourth round in New York 12 months ago.
He was beaten again in the last 16 in Australia this year in a five-hour epic where he had led 6-1, 5-2.
But his confidence is high -- in 2013, he is 7-7 against top 10 opponents; in the previous three years he was a combined 7-26.
"The match with Stan in Melbourne was one of the most exciting I have played on hard courts," said Djokovic, bidding to make a fourth successive New York final.
"In the past we knew that Stan had the quality to play well but not on a consistent basis. Now he has improved his movement and has a greater variety of shot. He is a very complete player."
Nadal heads into his fifth US Open semi-final boasting 10-0 record over fellow 27-year-old Gasquet.
Despite that dominance, Nadal knows that Gasquet is battle-hardened, having needed five sets to see off Milos Raonic in the fourth round, in the longest match of the tournament so far, and then fourth seed David Ferrer.
"I expect to him very good. He's playing a great tournament. Two great wins against Raonic and David. Five-set victories against tough opponents, that's brilliant for him," said Nadal.
French Open champion Nadal, by contrast, has been unbroken in 67 service games as he looks to win a 10th title of 2013 since his return from a seven-month injury layoff in February.
Gasquet, whose only other semi-final appearance was a run to the 2007 Wimbledon last-four, admits he is not a favorite, especially after Nadal dropped just four games in his quarter-final win over Tommy Robredo.
That was the fastest last-eight tie at the US Open in 25 years.
"We know that Rafa has the confidence and it's clear that it's going to be a very difficult match," Gasquet said. "I am not the favorite and to beat him it's not enough to be good, I have to be monstrous."