Cilic won the 2014 matchup in straight sets but this match resembled their 2010 second-round matchup in Flushing Meadows, when Nishikori rallied for a five-set victory in 4 hours, 59 minutes, the fifth-longest men's singles match by time in U.S. Open history.
Nishikori, the 21st seed, advanced with a 2-6, 6-4, 7-6 (7/5), 4-6, 6-4 victory over Marin Cilic - the man who beat him in the 2014 final.
The break proved less useful in week one to players toiling on outside courts - far away from the sanctuary of a locker room.
But, not to be denied, Djokovic broke straight back to take the match to enhance his ideal semi-final record in NY to 11 from 11.
Djokovic had the same sweaty sentiment.
The Swiss superstar, owner of 20 Grand Slam titles, said the suffocating humidity on Arthur Ashe Stadium played a role in the defeat.
"There are so many people that stayed at the stadium and its past midnight".
Naomi Osaka enjoyed a comfortable 6-1 6-1 win over Ukraine's Lesia Tsurenko to become the first Japanese woman in 22 years to reach the semi-final stage of a Grand Slam. At 2-2 in the second set Millman was allowed to leave the court to change his kit after the umpire ruled that the playing surface had become unsafe because of the floods of sweat dripping off the 29-year-old.
At least 20 dead as twin blasts hit Afghan capital
It is known for its heavy use of suicide bombers and was designated a terrorist organisation by the USA in 2012. More than 70 others were injured in the bombings, which targeted a wrestling club in the mostly Shiite area.
This year's edition has been fairly smooth sailing for Djokovic, who has only dropped two sets en route to the semis and has switched up a gear in his last three matches. She recovered to win in three sets, with her opponent accusing her after the match of acting.
It's another scorching hot day in NY and that means the extreme heat policy is back in effect for the third consecutive day at the U.S. Open.
Cilic responded strongly, noticeably raising his intensity, but the Croatian's serve broke down at a crucial moment as the set was decided in a tie-break.
The policy is a rule on the women's tour, but not the men's.
"This is a good sign for Millman that he's got him breathing heavy".
Osaka continued what has been a largely dominant run through the draw by winning in just 57 minutes, the third time in her five matches she didn't even have to play an hour. Cilic started well, taking the opening set and going up a break in the second.
The win meant that Djokovic advanced to his 11th straight United States semifinal - a streak only bettered by Jimmy Connors.
Federer, a 20-time Grand Slam champion, was ousted on Monday by John Millman, an unseeded player from Australia. Djokovic has clearly dominated the head-to-head with a 14-2 winning record, with Djokovic winning their last 13 meetings.
Amazon have exclusive rights to the final major of the year after outbidding Sky.
The Croatian has built on that success, reaching two more finals in the last two seasons, but Nishikori's only similar run came in NY two years ago when he defeated Andy Murray to reach the semi-finals before losing to Stan Wawrinka.