The 35-year-old Mannarino had gone five sets in his previous three matches.
But after missing a chance to break Djokovic's serve in the first game, he was never really close to threatening the Serb.
Djokovic has admitted that he has not felt fully fit in recent matches, but says his health is on the rise.
- The last few days have been really good.
It's going in the right direction, both health-wise and tennis-wise.
Now the quarter-finals await the 36-year-old, either against the Greek Stefanos Tsitsipas or the American Taylor Fritz, who meet in this now.
Highlights from the Australian Open
The Hungarian impressed with super shots: "Ridiculous"
35 sec
Match was canceled after the strange images
35 sec
The star vomited from the heat in Australia
11 sec
Here the world number one is eliminated
22 sec
Cameron Norrie defeated Casper Ruud
23 sec
Tsitsipas is celebrated after the unique stroke
33 sec
Osaka eliminated from the Australian Open in the return
31 sec
The qualifier knocked out Caroline Wozniacki
33 sec
Wimbledon champion outright eliminated
22 sec
Cori Gauff took home the victory in the Australian Open premiere
19 sec
Djokovic easily advanced - made the great player laugh
38 sec