First, Japan's Nishikori became the first man from Asia to reach a major singles championship match by staying fresher than Djokovic in stifling heat and winning 6-4, 1-6, 7-6 (4), 6-3.
Then, Croatia's Cilic used every bit of his 6-foot-6 frame to deliver stinging serves and flat groundstrokes during a quick-as-can-be 6-3, 6-4, 6-4 victory over Federer.
"It's fairly simple, I think: Marin played great and I maybe didn't catch my best day," Federer said after his 1-hour, 45-minute loss. "That's pretty much it in a nutshell."
So much for No. 1-seeded Djokovic facing the No. 2-seeded Federer in a matchup between men who have combined to win 24 Grand Slam trophies. In what some will see as signaling a generational shift in tennis, Monday's final will be No. 10 Nishikori against No. 14 Cilic.
"That's going to be a sensational day for both of us," said Cilic, who at 25 is a year older than Nishikori.
For the first time in nearly a decade -- since Marat Safin beat Lleyton Hewitt at the Australian Open in January 2005 -- a major final will be contested without at least one of Federer, Djokovic or Rafael Nadal, who didn't attempt to defend his 2013 US Open title because of a right wrist injury.
That trio won 34 of the past 38 Grand Slam trophies, including two months ago at Wimbledon, when Djokovic edged Federer in a five-set final.
"It's exciting for the game to have different faces from time to time," the 33-year-old Federer said. "It's definitely refreshing to some extent. It's big for Croatia; it's big for Japan."
Cilic, forced to sit out last year's US Open during a doping suspension, is the first man from Croatia to get this far at a major since his coach, Goran Ivanisevic, won Wimbledon in 2001.
That's nothing compared to Japan's wait.
As it is, Nishikori was the first man from his country to reach a Grand Slam semifinal since 1933.
"Very happy to make history," said Nishikori, who moved to Florida at age 14.
He weaved his way through a pair of five-setters totaling more than 8 hours against No. 3 Stan Wawrinka and No. 5 Milos Raonic, yet appeared much more lively as the temperature neared 100 degrees than Djokovic, a guy widely considered as fit as they come.
"Just wasn't myself," Djokovic said.
Especially in the pivotal third-set tiebreaker. He missed a pair of backhands. He double-faulted. He missed a forehand, and another to end the set, then smacked a ball in anger. Up in the stands, Nishikori's coach, 1989 French Open champion Michael Chang, rose to his feet and pumped his fists.
Making Nishikori's performance all the more impressive is that as recently as a few weeks ago, he was swinging a racket while seated in practice, unable to run because he had a cyst removed from the bottom of his right foot in August.
"I didn't even know if I should come to New York," he said, "so I wasn't expecting nothing, actually."
Chang refused to let Nishikori think that way.
"He might not have prepared the best way he knows how. But just because you haven't done that doesn't mean that you don't give yourself the opportunity to come out and play," Chang said. "That's why I told him, You get past the first round, the second round, anything can happen."
This unforeseeable US Open final shows that's true.
In the quarterfinals Thursday night, Federer dropped the first two sets against Gael Monfils and faced two match points, but escaped.
There would be no such comeback against Cilic, who worked to improve his game while sidelined after testing positive for a stimulant in May 2013. He said he ingested the substance accidentally via a glucose tablet; the International Tennis Federation sought a two-year ban but it eventually was reduced to four months.
Cilic had only played one previous major semifinal, at the 2010 Australian Open, while this was Federer's 36th. And Cilic came into the day with an 0-5 head-to-head record.
But this one went the other way. Wasn't even close.
Cilic hit serves at up to 132 mph and finished with 13 aces, including three in the final game. That he would serve effectively was no surprise. What truly stood out, though, was the way Cilic managed to hang with Federer in exchanges from the baseline.
"He played," Federer said, "with no fear."
Information from The Associated Press was used in this report.
Nishikori Into US Open Final
Kei Nishikori beat Novak Djokovic 6-4, 1-6, 7-6, 6-3 to become the first Asian man to reach a Grand Slam final.
Cilic Upsets Federer In Semifinals
Marin Cilic defeated Roger Federer in straight sets at the US Open to advance to his first Grand Slam title match.
Top-Seeded Djokovic Falls To Nishikori
Novak Djokovic talks about his loss to Kei Nishikori in the semifinals at the US Open.
I Expect Better From Myself
Roger Federer talks about his loss to Marin Cilic in the semifinals at the US Open.
Nishikori Stuns Djokovic
Prim Siripipat and Darren Cahill break down Kei Nishikori's upset over top-seeded Novak Djokovic to advance to the US Open finals.