The 10th seed from Japan pulled off one of the great shocks at Flushing Meadow on Saturday as he beat the world number one 6-4 1-6 7-6 (7-4) 6-3.
Nishikori will face either Roger Federer or Marin Cilic in the final on Monday after an outstanding display against top seed Djokovic in the searing New York heat.
He commented afterwards: "I was a little bit tight, especially with it being my first semi-final in a grand slam.
"It's just an amazing feeling beating the number-one player. They were tough conditions today. I guessed I would have to play a long match and hopefully I can recover well for the final.
"He started to play much better after the first set, more aggressive, but I tried to forget about the second set and focus again. Michael Chang has been helping me a lot, he is the reason I'm here. I hope it's big news in Japan. I feel the support from Japan, even on the TV."
The world number 11 had come through two five-set epics to reach his first major semi-final, but he was not forced to go the distance in a thrilling semi-final.
Djokovic, who was attempting to reach his fifth-consecutive final at Flushing Meadows, made 35 unforced errors as a clinical Nishikori took five of his seven break points in a win that represents his finest hour.
Nishikori was tested in his first service game before holding to ease the nerves at 1-1 and delivered a forehand winner in the next game after forcing Djokovic wide to secure the first break of the match.
The world number one responded in the next game by fashioning three break points and needed only one, as Nishikori went long.
Nishikori regained the initiative by breaking for the second time, earn three break points with a sublime backhand down the line and taking a 4-3 lead with a forehand which clipped the line.
The Japanese then held his nerve to serve out the set, but that appeared to serve as a wake-up call to Djokovic as he took the upper hand in the second set with a break to lead 3-1 as Nishikori fired a forehand into the tramlines.
Djokovic demonstrated that he was getting into his stride with a stunning drop-shot in his next service game and took a 5-1 lead with a second break when a poor drop-shot from Nishikori was punished.
The Serb served won the set with an ace, next service game and took a 5-1 lead with a second break when a poor drop-shot from Nishikori was punished.
Nishikori responded well in the third set, breaking to take a 5-3 lead with a sublime return after a fine cross-court forehand had earned him the break point.
Djokovic broke back immediately when Nishikori double-faulted and both players regained their composure to set up a tie-break.
Nishikori raced into a 4-0 lead in the tie-break and although the world number one clawed his way back into it at 4-3, the 24-year Japanese was not to be denied as he secured two more mini-breaks to take the set.
The intense heat tested both players to the limit, but Nishikori appeared to coping better as he broke at the start of the fourth set when Djokovic got a forehand all wrong.
Nishikori held his nerve to hold in each of his service games and fashioned two match points on Djokovic's serve, of which he took the second when the Serb's forehand was long and the 10th seed was left to celebrate a famous victory.