Nadal again took his time to grind out the win but he continued his straight-set form which has seen him not drop a set so far this tournament.
It was all started when leading 2-0 in the first set, Mannarino's default serve was defended by Federer in an nearly "cricket" style.
Federer's progress through the draw has been smooth and serene, not dropping a set nor losing a service game on his way to an Open era record 53rd Grand Slam quarter-final.
Like Nadal, who could strike Djokovic in the semis, Federer hasn't dropped during his charge to a 16th Wimbledon quarter-final, nearly surely a staggering record that will never be surpassed.
Federer defeated Frenchman Adrian Mannarino 6-0, 7-5, 6-4 to reach his 16th Wimbledon quarter-final.
"It was important for me to stay focused". I'm a big player, big serve.
"The expectations he's had to deal with for over a decade, 15 years, I mean, at the top of the game, he's able to deal with it so well, which isn't easy".
"It's definitely helped a certain style of player, maybe the big servers", said 20-time major victor Federer.More news: USA softens stand on Iran oil; relaxation for India
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Djokovic is the man in the shadows at Wimbledon, reprising a role he has grown accustomed to while the crowd gush over Federer and Nadal.
The cricketing body also chose to indulge in some banter and quickly responded to Wimbledon's Twitter handle about ranking Federer as the number one Test batsmen in the world.
It will be Djokovic's 41st appearance in a Grand Slam quarterfinal and he will start favorite against Nishikori who will be in his first last-eight at the All England Club.
With Kevin Anderson taking nearly three and a half hours to tame French showman Gael Monfils in the previous match, Djokovic knew he had about two hours of daylight left if he wanted to avoid coming back on Tuesday's rest day to finish off the contest.
Now the Argentine faces two-time Wimbledon champion Nadal, who allowed him just six games when they last met in the Roland Garros semi-finals in June.
Nadal reached the quarterfinals of Wimbledon for the first time since 2011 after defeating Jiri Vesely in a 6-3, 6-3, 7-5 victory on Monday.
A pretty emphatic win against an opponent who had no answers on the day, Fed had too much pace of shot, too much guile and too much aggression.