The 22nd-seeded Mannarino became the first man to earn a break point against Federer at the tournament, but was unable to take any of his four opportunities.
The 36-year-old is also on a streak of 32 consecutive sets won at the tournament, just two off his record.
The menace was back in Djokovic's eyes, and he took this momentum with him when seeing off Karen Khachanov in straight sets on Monday.
"That's how important Wimbledon is to me and to us over here".
South African tennis player Kevin Anderson. Depends against who you play you have less or more chances to win.
Seven-time champion Serena Williams advanced to the Wimbledon semifinals with a 3-6, 6-3, 6-4 victory over Camila Giorgi of Italy.
The seventh-seeded player was defeated by Kiki Bertens 6-3 7-6.
Since seeds were introduced in the 1920s, it's the first time none of the top-10 have reached the women's quarterfinals at Wimbledon.
But the Argentine broke back immediately with a volley and then saved another break point at 5-5 with an ace.
The Swiss maestro swept away his opponent Adrian Manarinno in three sets, but it was a nonchalant flow of the racket in the third set which caught the eyes of willow-lovers. "I knew he was much better than that first set and he showed that".
The 12th-seeded Ostapenko was aggressive throughout, hitting 28 winners - 13 coming off her backhand.
It will be 32-year-old Nadal's 35th appearance in a Grand Slam quarter-final as he continues his bid to win an 18th major title.
Federer said afterward that he never got ahead of himself despite winning the first set 6-0.
"It was great to win that first set so quickly", Federer told the BBC.
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.
"So far four matches have been really, really good for me", said Djokovic, who also eliminated British number one Kyle Edmund in the third round.
Federer plays Anderson on Wednesday after the eighth seed edged flamboyant Frenchman Gael Monfils 7-6 (7-4) 7-6 (7-2) 5-7 7-6 (7-4) in one of the matches of the championship.
Three times he was scheduled last on court, putting him at risk of falling victim to fading light with the burden of having to return the following day.
In a sense, it is one more bullet point that belongs on the list of Federer's contributions to tennis when he retires: 20 Grand Slam titles (and counting); eight Wimbledon titles (and counting); and unofficial coach and mentor to the next generation that both reveres and hopes to supplant him one day, as he did Sampras almost two decades ago.