Federer faces eighth seed Kevin Anderson, who he has not dropped a set against in four previous meetings.
Soon enough, Djokovic was on his way to the semi-finals, where he will meet Rafael Nadal. His record of 34 straight Wimbledon wins when up 2-0 was snapped in the third set, and Federer fell shortly after.
With fifth-set tiebreakers not permitted at Wimbledon, they played on - each point heavy with implications.
No tournament wants to see Federer go out and we'll be denied a repeat of that 2008 Federer v Nadal final, which is a shame. Anderson and Federer are knotted at 3-3 in the final set.
"Down two sets to love I tried my best to keep fighting". "By the end, I thought I did a great job of not thinking about things too much". Beating Roger Federer here at Wimbledon will be one I remember, especially in such a close match. It's one of those average days you have to try to win the match, and I just couldn't get it done today.
"It would take an unbelievable serving performance and for Roger had a bad serving day to cause an upset". "I probably won't have another 6-0 set this week, so I'll enjoy this one". As the match went on, I gave it my all.
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.
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Nadal faces the victor of Juan Martin del Potro and Gilles Simon while Federer takes on US Open finalist Kevin Anderson in the quarterfinals. Djokovic grunted and groaned, he took on chair umpire Portugal's Carlos Ramos, who he accused "of double standards", and was handed two code violations, in the second and fourth sets, for racket abuse and time violations, but he also produced razor-sharp tennis. In all, the two battled it out for over four hours. Raonic never broke Isner's serve, and while Isner broke Raonic's serve just three times, it was just enough to move on. Of course, the goal is to come back here next year.
"Rafa [Nadal] and Roger played all four matches on Centre, myself only one". It's the second-farthest he's advanced in a Grand Slam tournament, having made the final of the US Open in 2017. Since then, it has been a long rehabilitation process.
Anderson appeared in his first Grand Slam, the Australian Open, in 2008.
Federer had breezed into the quarter-finals without dropping a set for the eighth time and was imperious in the opening set in which he hit 10 winners and only three unforced errors.
"I felt great in practice, good in the warm-up".
He's playing like it, at least.
Anderson held his nerve with his relentless and powerful serve win the fourth and send the rip-roaring contest into an unlikely fifth and deciding set. The 31-year-old, however, served up the whole range from antics to awesome shot-making. He'll need to keep up that consistency, but at this point he's eyeing his fourth career Wimbledon title and 13th Grand Slam.