The Japan 10th seed won 6-4 1-6 7-6 (7-4) 6-3 before Croatian Cilic completed a big day of upsets at Flushing Meadows with a 6-3 6-4 6-4 over 17-time Major winner Roger Federer.
Here is a selection of the best Twitter reaction from the professionals and celebrity tennis fans to a fascinating day of US Open action on Saturday.
Former Tottenham chairman Lord Sugar (@Lord_Sugar) is stunned by the shock result: “It’s sayonara Djokovic as the first Japanese male player Nishikori gets into the final of the US open”
— Sabine Lisicki (@sabinelisicki) September 6, 2014
Former Australian tennis player Darren Cahill (@darren_cahill) tweets a fantastic stat: “Not sure (?) but I think the last time a Grand Slam final did not feature either Nadal, Murray, Federer or Djokovic was 2005 Australian Open”
Hull City midfielder Tom Huddlestone (@Huddz8) confirms that the big three have finally been caught: “Just seen this ——The last Grand Slam final that didn’t involve Federer, Nadal or Djokovic was the Australian Open 2005. #tennis #usopen”
Meanwhile, tenth seed Caroline Wozniacki (@CaroWozniacki) looks back ruefully at a photo posted by Serena Williams earlier this summer: “#Repost from @serenawilliams — The hat says it all ohh yeah!! can’t wait!!”
2003 US Open champion Andy Roddick (@andyroddick) is shocked by the big upsets: “Wow”
Liverpool defender Dejan Lovren (@DejanLovrenLFC6) is thrilled for his fellow Croatian: “Bravo @cilic_marin !! Good luck in the finals, we are with you! #USOpen2014”
Djokovic’s coach Boris Becker (@TheBorisBecker) vows the world number one will be back: “Djokernole will be coming back !!!”
Patrick McEnroe (@PatrickMcEnroe) claims to have seen this final match-up coming: “Oh I had this final in my @usopen bracket didn’t you?”
MORE: The latest football news
MORE: The latest tennis news
BIOGRAPHY: Ethan Hazard
BIOGRAPHY: Daniel Sturridge