Djokovic is expected to come through comfortably, although Millman knocked out world No 2 Federer in four sets in the fourth round.
Should Djokovic progress, he will face Kei Nishikori, who was pushed hard by Croatian Marin Cilic before prevailing in five sets.
Djokovic has reached the semi-finals in each year he has played at the US Open since 2007 so he will fancy his chances.
But Federer fears for Djokovic especially if the humidity climbs during his clash with Millman.
He said: “I love his intensity. He reminds me of David Ferrer and those other guys that I admire a lot when I see them, when I see how they train, the passion they have for the game.
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“He has options now, especially where it’s a bit slower, to return in and return back.
“I think against Novak, he just has to bring it again, try to worry Novak, hope for another hot day.”
Meanwhile, Millman isn’t ruling out taking another big scalp at Flushing Meadows.
He said: “Yeah, why not?
“Again, I’ll have to improve a lot on the last time I played him. He’s an incredible player.
“I think he’s in some really good form right now, too.
“Yeah, but why not? I think it’s a disservice to who I am if I go out there and don’t have that belief.”
Novak Djokovic vs John Millman LIVE
(*denotes serve)
*Novak Djokovic 5-2 John Millman
Djokovic digging deep, but he holds after he mixes up his serve with a slower one and Millman’s forehand sails out. Djokovic also got his fifth forehand winner with a terrific shot down the line from behind the baseline.
Novak Djokovic 4-2 John Millman*
Djokovic loses a gripping game that lasted well over 15 minutes. Millman had a double fault, but there were some touches of class including a beautiful double-handed cross-court backhand. Millman getting to grips with the assignment.
*Novak Djokovic 4-1 John Millman
Djokovic rarely troubled so far. He had to flick a shot into the open court when Millman tried to play a slice down the line that landed awkardly, but Djokovic varying up his serve nicely.
Novak Djokovic 3-1 John Millman*
A couple of errors coming off the backhand of Djokovic’s racket. Millman took more of a risk with some bigger body shots and he’s on the scoreboard.
*Novak Djokovic 3-0 John Millman
Djokovic giving Millman plenty to think about. Millman fires long with his backhand and he is yet to hit a winner in these opening few games.
Novak Djokovic 2-0 John Millman*
Djokovic needed two bites of the cherry to get the break. Some fabulous stuff and Djokovic making it physical. One point contained a 26-shot rally and one was a 27-stroke rally. Djokovic looking good on the short ball and is turning defence into attack very quickly.
*Novak Djokovic 1-0 John Millman
Pretty comfortable hold of service in the opening game for Djokovic. Some lovely touches, coming forward in the early stages and clinches the game with a straight forward forehand volley into the open court.
1:55am: Djokovic and Millman going through the paces during the warm-up. We’ll be underway shortly.
1:45am: Djokovic has faced Millman just once before in his career so they won’t know too much about each other.
1:40am: Madison Keys has just knocked out Carla Suarez-Navarro and is through to the US Open semi-finals, but it was a bit of a subdued atmosphere on the Arthur Ashe Stadium court. Hopefully it will be a bit more lively for Djokovic vs Millman.
1:35am: Good morning to those who are still awake in the UK. Welcome along to our overnight coverage of Novak Djokovic vs John Millman. This will be a tricky encounter. I did say that Roger Federer was a dead cert against Millman, but I was forced to eat my words, so I’m making no predictions. What do you think? Djokovic in straight sets?