The Serbian, who has endured a rough 12 months both on and off the court, produced a performance of real quality to hint that he is over his troubles against the Frenchman Mannarino, who gave a good account of himself but simply could not cope with Djokovic's ability to return balls when he seemingly has no right to do so.
Yet treatment on an injury seemingly to his right arm and shoulder in the third set will raise fears ahead of his last eight clash with Tomas Berdych on Wednesday [12 July]. The 12-time grand slam champion underwent treatment on the problem deep into his three-set win and it remains to be seen whether it will affect his attempts to win a fourth title at SW19.
"We'll see on the shoulder," Djokovic told the BBC. "It has something which has been dragging back and forth for a while but I am still managing to play. There are no clear favourites any more.
"I'm glad it's all done and looking forward to the next one I haven't dropped a set yet on grass, I have been feeling really good. I am motivated to go as far as I can, it's one of my favourite tournaments."
Djokovic wavered a little on his opening service game but overpowered Mannarino to break him at the first time of asking. From there, the three-time Wimbledon champion wrapped up the set in comfortable fashion, breaking the world number 51 once more and holding firm on his own serve to win 6-2.
The second set started in similar fashion, Djokovic managing to break his opponent's serve with little fuss, but Mannarino came roaring back to break his illustrious counterpart and take the second set to a tie-break, something that seemed incredibly unlikely during the opening exchanges.
Mannarino smelt an opportunity and pushed the former world number one hard as he attempted to make the clash under the Centre Court roof interesting, but Djokovic clinched the tie break 7-5 to all but confirm his passage into the last eight at SW19.
The third set followed the same pattern as the ones that preceded it. Despite needing the physio to treat a niggle in his upper arm, Djokovic swiftly re-asserted his dominance and broke Mannarino during the embryonic stages of the set and ventured to the net more often in order to lessen the pressure on his troubling arm injury.
The champion from 2011, 2014 and 2015 was clearly in some discomfort during the dying embers of the clash but reminded onlookers, who were lucky to be watching Djokovic due to a schedule change caused by Rafael Nadal's gruelling loss to Gilles Muller, of his supreme flexibility and battling qualities, which he will need more of if he is to get his career fully back on track at the All-England Club.