Djokovic is expected to come through comfortably, although Millman knocked out world No 2 Federer in four sets in the fourth round.
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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.
“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 updates
*Novak Djokovic 6-3, 6-4, 2-1 John Millman
Djokovic has carved a break for himself and he’s forcing more errors out of Millman despite the punishing rallies.
*Novak Djokovic 6-3, 6-4, 1-1 John Millman
Djokovic pushed hard in that game but he finishes with a drop half volley. Djokovic wants to get this over and done with.
Novak Djokovic 6-3, 6-4, 0-1 John Millman*
Millman comfortably holds his serve and is asking more questions of Djokovic.
*Novak Djokovic 6-3, 6-4 John Millman
Djokovic holds his nerve. There was a delicate drop shot and the two-time US Open champion is looking good now. Millman faces a tall order to turn this around.
Novak Djokovic 6-3, 5-4 John Millman*
This is turning to be a battle of the wills. Djokovic has the game gift-wrapped when Millman double faults. He’s now serving for a two set advantage.
*Novak Djokovic 6-3, 4-4 John Millman
We’re back level again. Djokovic gets away with a net chord and Millman can only dump his shot into the net.
Novak Djokovic 6-3, 3-4 John Millman*
Djokovic wastes a break point, plays a sloppy drop shot that Millman latches onto and Millman is pumped after clinching the game. Nearly one hour and 45 minutes on court and Djokovic is changing his socks.
*Novak Djokovic 6-3, 3-3 John Millman
Djokovic finishes off in style with a cross-court backhand to trick Millman. Some high quality points from the Serbian there.
Novak Djokovic 6-3, 2-3 John Millman*
Djokovic didn’t look too refreshed after the 10-minute humidity break. A loose drop shot and a mishit forehand helps Millman hold.
*Novak Djokovic 6-3, 2-2 John Millman
Djokovic finishes off the game with a cross court forehand. The humidity causes a frosty exchange between Djokovic and Millman with the latter going off court to change his top.
Novak Djokovic 6-3, 1-2 John Millman*
Djokovic looking a little unsettled and missed the forehand that almost saw him fall over. Millman has warmed to the task and is ahead now in the second set.
*Novak Djokovic 6-3, 1-1 John Millman
Djokovic is digging deep once again, but he’d forcing the issue and levels up at the start of this set.
Novak Djokovic 6-3, 0-1 John Millman*
Another bruising game. Djokovic looked weary at stages and even missed a simple volley. Millman holds serve with an ace.
*Novak Djokovic 6-3 John Millman
Another topsy-turvy game. Djokovic missed a smash from the baseline that he thought was drifting line and he looked a little tired, but clinches the first set as he draws an error from Millman on his second serve to the ad court.
Novak Djokovic 5-3 John Millman*
Millman drew some errors from Djokovic. There was a tired drop shot from Djokovic and while he got away from it, he was asked more questions and he will have to serve it out for the set.
*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?