Djokovic takes a staggering 25-2 career record over Czech 11th seed Tomas Berdych into his quarter-final as he eyes a potential semi-final duel with Federer.
Federer, who is yet to lose a set in this year's tournament, regained some form of revenge for last year's defeat to the Canadian at the semi-final stage in emphatic fashion with a 6-4 6-2 7-6 win in under two hours.
Since 2002, the Big 4 comprising of Federer (7), Nadal (2), Djokovic (3) Andy Murray (2) have won every Wimbledon crown.
Three-time victor Djokovic was also heading for the exit after the second seed quit his quarterfinal against Tomas Berdych with a right elbow injury while trailing 7-6 (2), 2-0.
American Sam Querrey will play Croatia's Marin Cilic in the other semi-final.
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Roger Federer is coming off a straight sets win over Milos Raonic that took 31 games to decide.
Despite being the most successful player in the history of the men's game, there had been little in Federer's play between 2013-16 that screamed he was capable of winning multiple grand slams in the same year again. 'I saw things very well. They are bigger and stronger than me. Djokovic hasn't yet lost a set in this year's edition of Wimbledon.
"I think also for the spectators it's more enjoyable to watch because it's such a name like Federer, Murray, huge names, and I think they deserve obviously to be on Centre Court and Court One". "It's big for him to step out on court and give it a go, even though maybe knowing, like me past year, that chances are slim he was going to defend this title".
Federer believes he has found the ideal balance, playing at the right times and resting when required.
He will become the first man to win the title eight times if he qualifies and wins in Sunday's final.
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The five-time champion at the All England Club advanced to the last four for the second year in a row by beating Jelena Ostapenko 6-3, 7-5 Tuesday under a closed roof on Centre Court.
Twenty-year-old Ostapenko, who won the French Open last month, felt cosy Court 12 was too small for her clash with Elina Svitolina. That said, Berdych did beat Federer in the quarterfinals here in 2010, a time when Fed-Ex had won six of the previous seven tournaments at the All-England Club.
Roger Federer has declared himself fit and raring to go after he did what Andy Murray and Novak Djokovic could not by cruising through to the Wimbledon semi-finals. Against a player like Raonic, who can blow just about anyone away with his serve, those kind of tactics often prove correct.
42 - The number of Grand Slam events it took Sam Querrey to reach his first Slam semi-final.
"I was sort of moving on, let's see if he can do it again".
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"I tried", he said.