The Serbian superstar recaptured his top form to surge into the last 16 after dropping sets in his opening two matches while feeling ill, and he stepped up another level against Adrian Mannarino.
The French 20th seed, who at 35 is a year younger than Djokovic, has been enjoying a late career resurgence.
But he was taught a lesson by the world number one, who won the first 13 games in powering through to the last eight of a Grand Slam for the 58th time, equalling Roger Federer's men's record.
"I played great, from the first to the last point," said the defending champion, who is red-hot favourite to collect an 11th Melbourne title and a record 25th Grand Slam crown.
"It's going in a positive direction, health-wise, tennis-wise so I'm really pleased with where I am at the moment."
Djokovic almost always plays the night session on Rod Laver Arena, but was bumped to the afternoon this time.
That's because home hope Alex de Minaur, seeded 10, is bidding to make the last eight for the first time, with Russian fifth seed Andrey Rublev standing in his way.
In other fourth-round action, in-form fourth seed Jannik Sinner faces last year's semi-finalist Karen Khachanov.
The man who beat him in that semi-final, Stefanos Tsitsipas, who is the seventh seed, takes on 12th-seeded American Taylor Fritz for the right to meet Djokovic next.
Defending women's champion Sabalenka has been in imperious form and was in complete charge against unseeded Amanda Anisimova on Margaret Court Arena, sweeping past the American 6-3, 6-2.
Fourth seed Coco Gauff, attempting to become the first woman to back up a US Open title with a Grand Slam win in Australia since Naomi Osaka in 2018-19, has been almost as impressive.
She swatted aside Poland's unseeded Magdalena Frech 6-1, 6-2 in just 63 minutes on Rod Laver Arena, with the 85-year-tennis legend watching from the stands.
"It was an honour to play in front of you, so thank you for coming to my match," said 19-year-old Gauff, who had never progressed beyond the fourth round at Melbourne Park in four previous attempts.
"First Aussie quarter-final. Super happy to be in this position and be here.... It's cool to get over that hump."
She will next meet Ukraine's Marta Kostyuk, who beat Russian qualifier Maria Timofeeva 6-2, 6-1.
With seven of the women's top 10 seeds knocked out in the first week, including world number one Iga Swiatek, both Gauff and Sabalenka have a glorious chance to win their second major major title.
They are on the same side of the draw and will not meet in the final, with a potential last-four clash looming instead.
Sabalenka has dropped just 11 games in four matches and is favoured to win another title to go with her breakthrough Grand Slam crown last year.
Should she go all the way, the 25-year-old will be the first woman to retain the title since compatriot Victoria Azarenka completed the feat in 2013.
"I'm getting stronger because I enjoy the atmosphere and I really want to stay here as long as I can till the very last day," she said.
Her next opponent will be unseeded Russian 16-year-old Mirra Andreeva or ninth seed Barbora Krejcikova.
If Andreeva keeps her dream run going, she will become the youngest woman to reach the Melbourne Park quarter-finals since Martina Hingis in 1997, a player she has often been compared to.