Djokovic led Jo-Wilfried Tsonga 6-3 6-2 in Arthur Ashe Stadium when his opponent pulled out with a left knee injury and confirmed the Serb's passage to the semi-finals.
He will face 10th seed and another Frenchman Gael Monfils, who had earlier beaten compatriot Lucas Pouille 6-4 6-3 6-3.
Djokovic has now spent just six hours and 28 minutes on court at Flushing Meadows after earlier withdrawals from Jiri Vesely and Mikhail Youzhny.
Tokyo 2020 men's doubles
Andy Murray / Joe Salisbury v Marin Cilic / Ivan Dodig - Watch live
Andy Murray, by contrast, has already played nine hours and 32 minutes, with the Scot's quarter-final match against Kei Nishikori on Wednesday still to come.
The extra rest has proven timely for Djokovic, who arrived in New York nursing injuries to both his left wrist and right elbow. The top seed is not worried about any lack of rhythm.
"I am not really concerned," Djokovic said.
"Actually, in this stage of the season, considering some physical issues I have had in the last month, month and a half, this was the scenario that I needed and I wished for.
"I got a lot of days off and recovered my body. Right now I'm feeling very close to the peak. That's the position where I want to be. This scenario was ideal at this stage."
Djokovic has been reluctant to discuss the impact of his physical problems and when asked if his peak referred to fitness or form he said: " I'm reaching my peak in terms of my form."
Monfils brushed aside Rafael Nadal's conqueror Pouille and has now advanced to his first grand slam semi-final since the French Open in 2008.
The flamboyant 30-year-old is yet to drop a set in this tournament but he has struggled against Djokovic in the past, losing all of their last 12 meetings.
"I love watching Gael," Djokovic said. "He's one of the few players that I will definitely pay a ticket to watch.
"He's very charismatic. Plays with a smile. Enjoys tennis. Enjoys life. But also he seems more focused at this time of his career.
"Especially on the hard court this year maybe he's playing the best tennis he ever played. I'm d efinitely expecting a tough battle."
Monfils has been renowned more for his showmanship than results - he stopped to tie his shoelaces mid-point against Marcos Baghdatis in round four - but insists he is not becoming boring in his old age.
"I always say if I have the ball I do it because I love it," Monfils said.
"I think when I dive on the court I dive not for people. Come on. To be honest, am I going to hurt myself for people? No.
"I dive because I want to win the point. When you make the show, honestly, it's to entertain but it's to win."
In the other quarter-final match on Wednesday, the unseeded Juan Martin del Potro plays world number three Stan Wawrinka.
Thiem still 'several weeks' away from return, putting US Open defence in doubt
With Osaka and Barty out, who will win gold in wide-open women's draw?