The nine-time champion's damaged left hamstring has dominated discussions around his chances of triumphing again at Melbourne Park but there were no signs of discomfort here as he eased to a 6-2 6-1 6-2 victory with a ruthless display.
It was a very uncomfortable evening, though, for De Minaur - the last remaining home singles hope - on Rod Laver Arena as he was outplayed in all areas.
Watched by his girlfriend, British player Katie Boulter, the 23-year-old tried his best to find a way into the contest but, with no big weapons, he was simply unable to hurt Djokovic, who broke serve six times and did not face a single break point himself.
Speaking on court, the fourth seed said: "I cannot say 'I'm sorry you haven't watched a longer match'. I really wanted to win in straight sets. I thought the first four, five games were quite close.
"I started feeling I guess more loose, more free, to go through the ball and be more aggressive. I kept my focus all the way through and played the best match of this year so far."
On his hamstring, Djokovic said: "I didn't feel anything today. Today was great. I thank my medical team, thank God, anybody that really helped me.
"I don't want to celebrate too early. I know things can change really quickly and I don't take anything for granted. I'm really pleased today with the way I moved today and the way I hit the ball."
Djokovic will next take on fifth seed Andrey Rublev, who won one of the matches of the tournament against 19-year-old Holger Rune.
The Dane arrived at Melbourne Park as the hottest young prospect in men's tennis and looked set to reach his second grand slam quarter-final.
But he was unable to serve out the match in the fifth set, missed two match points on Rublev's serve at 5-6 and then squandered a 5-0 lead in the deciding tie-break.
As the tension ramped up on Rod Laver Arena, Russian Rublev then missed two match points of his own only for the ball to dribble over the net on his third chance, giving him a 6-3 3-6 6-3 4-6 7-6 (9) victory.
Rublev dropped flat on his back behind the baseline before apologising to his young opponent.
"It's not a roller coaster, it's like they put a gun to your head," said the 25-year-old.
"I never in my life was able to win matches like this. It's something that I will remember for sure all my life. I have no words, I'm shaking. Now I can go to the casino. If I (bet), for sure I'm going to win."
It was the cruellest way for Rune to lose, and the ninth seed said: "Of course, it's not the end of the world, but it hurts.
"It was super close. I had my chances. He played well, as well. The match points, nothing really to do. The luck was on his side. I think I did a lot. I fought until the end."
The other last-eight clash in the bottom half will be an unexpected all-American affair between 25-year-old Tommy Paul and 20-year-old Ben Shelton.
Big-serving Shelton has put together an amazing run at not just his first Australian Open but on the first trip of his life outside the US.
He claimed a second five-set win of the tournament, beating countryman JJ Wolf 6-7 (5) 6-2 6-7 (4) 7-6 (4) 6-2.
Shelton, who is still in college, said: "It's definitely a surprise. I got on the plane with no expectations. I know that it's very hard to adjust to Australia from the United States just with the jet lag, time change and everything.
"Never being out of the United States, I knew it would be a struggle. So I think it maybe has helped me a little bit kind of not having that expectation or the feeling that I have to perform, but being able to just go out there, be myself and play free."
Paul, ranked 35, made it three Americans through to the last eight with a 6-2 4-6 6-2 7-5 victory over Andy Murray's conqueror Roberto Bautista Agut.
â 13th #AusOpen quarterfinal— #AusOpen (@AustralianOpen) January 23, 2023
â 54th Grand Slam quarterfinal
Novak Djokovic doing Novak Djokovic things at Melbourne Park!@DjokerNole • @wwos • @espn • @eurosport • @wowowtennis • #AO2023 pic.twitter.com/ALmZZjxwal