After Nadal easily brushed aside Joao Sousa, defending champion Djokovic made light work of Ugo Humbert 6-3 6-2 6-3.
Federer rounded off the day on Centre Court, easily dispatching world number 20 Matteo Berrettini to claim his 99th win at the grand slam.
The eight-time champion will face Kei Nishikori, who got the better of Mikhail Kukushkin 6-3 3-6 6-3 6-4.
Djokovic will go up against David Goffin, while Sam Querrey's 6-4 6-7 (7-9) 7-6 (7-3) 7-6 (7-5) win over compatriot Tennys Sandgren means he will play Nadal.
Milos Raonic succumbed to Guido Pella in a tightly contested five-set encounter, with Roberto Bautista Agut making up the last eight.
Welcome to the last eight club, @guido_pella
— Wimbledon (@Wimbledon) July 8, 2019
FEDERER NEARING WIMBLEDON MILESTONE
No player has ever reached a century of wins at a single grand slam, but after breezing past Berrettini 6-1 6-2 6-2 in 74 minutes Federer is one victory away from doing just that.
The 37-year-old was in supreme form against the Italian - 14 years his junior - with Berrettini making a number of rookie mistakes in a humbling defeat.
Eighth seed Nishikori will be Federer's opponent in the quarters after he edged past Kukushkin in four sets.
"I think it's going to be tough. I remember some of the slams recently he arrived into the later stages with maybe some tough matches going into it. So far it's been really easy for him," Federer told a news conference when asked about Nishikori.
INEXPERIENCED HUMBERT HARDLY TESTS DJOKOVIC
Playing for the first time in the second week of a grand slam, 21-year-old Humbert offered little resistance as Djokovic took another step towards defending his crown.
Humbert found himself chasing the 15-time major winner for the majority of the match, which was wrapped up when a delightful drop shot set the Serbian up to serve it out.
"I played against a very talented player who made some big wins this tournament and definitely has a potential to reach big heights in tennis because he's got quite [an] all-around game," Djokovic told a news conference.
— Novak Djokovic (@DjokerNole) July 8, 2019
BULLISH NADAL LOOKS RAMPANT
French Open champion Nadal proved untouchable for Sousa, as the world number two cruised to a 6-2 6-2 6-2 victory on Centre Court.
Nadal hit 30 winners and converted six of eight break points in the win, which took an hour and 45 minutes.
With Federer and Djokovic likely to join him in the last four for the second straight slam, the third seed reflected on their lengthy period of dominance.
"It is special what we achieved in the last 15 years," Nadal said. "Something special, difficult to repeat I think, so many titles between three players."