Millman failed to reproduce the form he showed against Federer to send the Swiss parking, Djokovic showed class to march on.
Djokovic will meet Japan's Kei Nishikori in the last four having already swatted aside Hungary's Marton Fucsovics, American Tennys Sandgren, Richard Gasquet of France and the Portuguese Joao Sousa.
"I personally have never sweat as much as I have here", he said.
It's been so unusually muggy that the U.S. Tennis Association, which runs the Open, made up a rule on the fly to offer some help to the men, letting them take a 10-minute break between the third and fourth sets of a match that goes that long if it's too hot.
The Wimbledon champion has appeared more impressive with each passing round and will be up against a confident Millman who is unseeded but flying high after stunning Swiss second seed Federer in the previous round.
"Whatever the humidity is on outer courts or in the city", Isner said, "I think it's amplified on centre court".
Serbian sixth seed Djokovic, who will cap the night session, is in familiar territory, appearing in his 11th quarter-final at Flushing Meadows, and looks like a favourite with five-times victor Roger Federer knocked out of his half of the draw.
"It's fantastic to have the roof but it feels like a sauna".
The Wimbledon champion has struggled in the unusually extreme conditions in NY this year and was again in discomfort during a 6-3 6-4 6-4 victory over Australian John Millman that lasted almost three hours.
"I'd picked up a little injury in Cincinnati (in early August) and wasn't really happy".
The 29-year-old Tsurenko, who had struggled with the heat during her three-set win Monday over Marketa Vondrousova, grabbed her legs several times during the match, but did not ask for any medical help.More news: Dead, 4 Wounded in Shooting at Alabama McDonald's
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It was an impressive effort on Millman's part, but it's nothing Djokovic isn't used to.
Suarez Navarro has now lost all seven Grand Slam quarter-finals she has contested.
"I watched the second part of the match and Roger was not playing well".
"He doesn't miss a lot himself, so he just runs left, right, gets a lot of balls".
"He is truly a great fighter and had an fantastic tournament".
The pair, both shy characters, have recently become friends, and Nishikori said: "I hope people were watching us today". Millman said, "He makes you work hard for every point and it's relentless".
"It's great to see", said Nishikori, who is into his third major semifinal - all in NY - but is still in search of his initial Slam trophy.
"She has won a Masters". That break seemed to give Djokovic some much-needed rest and he sat down on his sideline bench without a shirt on and cooled off.
"I'm really excited for that (the Australian Open)".
"With tennis, each time you have to start from scratch and if you don't have a whole lot of money, which I definitely didn't, starting from scratch and going back to the grind is physically and mentally quite challenging".