An 11th title in Melbourne would take Djokovic clear of Margaret Court’s all-time record number of 24 Grand Slam wins.
Djokovic had dropped sets in the first two rounds and said he was struggling with an illness but found form against Tomas Martin Etcheverry in the third round.
However, he repeatedly came out on top against Mannarino, whose three previous matches in the tournament had all been won over five sets, by forcing long rallies.
“The last couple of days have been really good,” Djokovic said.
“It is going in a positive direction health-wise and tennis-wise so I am really pleased with where I am at the moment.
“All in all, a great performance.”
Up next for Djokovic is Fritz, who beat Greek seventh seed Tsitsipas 7-6 (7-2) 5-7 6-3 6-3 to reach his first Australian Open quarter-final.
Fritz and Djokovic met in the third round of the 2021 Australian Open, with the Serb winning in five sets.
Djokovic has won all eight of their previous matches, including a straight-set victory at the 2023 US Open.
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