The title match on Monday will be the first grand slam decider not featuring any of tennis's so-called big three - Federer, Rafael Nadal and Djokovic, since Marat Safin beat Lleyton Hewitt at the 2005 Australian Open.
Both Nishikori, and Cilic, have overcome major career setbacks to qualify for their maiden grand slam finals.
"I don't know what's going on,
It's an amazing feeling beating the world No.1 player.
I was a little bit tired, especially because it was my first time in a grand slam semi-final.
It was really tough conditions today. It was heavy, but I guess I love to play long matches and I hope I can recover for the final."Nishikori said.
Cilic, a former Australian Open semi-finalist who has twice previously made the last eight in New York, is back on a mission after sitting out last year's tournament while serving a reduced four-month suspension for testing positive to a banned substance.
Now Cilic is one win from doing so after crushing Federer in straight sets.
Nishikori, seeded 10th, upset the 2011 U.S. Open champion from Serbia 6-4, 1-6, 7-6 (7-4), 6-3 in 2 hours and 51 minutes.
After a rain delay, No. 14 seed Marin Cilic of Croatia then showed No. 2 Roger Federer the exit 6-3, 6-4, 6-4 to advance to his maiden major final.