(CNN) - In unfamiliar surroundings at Wimbledon, Roger Federer suffered an unfamiliar defeat against a big server who just didn't flinch.
Federer blew a match point and two-set lead to Kevin Anderson, 2-6 6-7 (5-7) 7-5 6-4 13-11, in a four-hour, 14-minute quarterfinal played away from his backyard of Centre Court on Wednesday.
His great rival, Rafael Nadal, narrowly avoided an upset to conclude the day, coming from behind to top Juan Martin del Potro in an even more mesmerizing 7-5 6-7 (7-9) 4-6 6-4 6-4, nearly five-hour slugfest.
Those who stayed behind on Centre Court to watch that one instead of England's semifinal against Croatia at the World Cup at the same time were thus highly rewarded.
The 17-time grand slam champion set a blockbuster clash with the rejuvenated and more rested Novak Djokovic. Djokovic, who owns 12 majors, had a relatively straight forward outing, prevailing 6-3 3-6 6-2 6-2 over Kei Nishikori in two and a half hours to begin the festivities on Centre.
Federer, unusually, won't be in the last four at Wimbledon.
"It's disappointing losing the next two sets after winning the first two and having match points," Federer told reporters. "I've been there before. I know what kind of energy I need to bring to the fifth. I was able to bring that.
"I didn't feel mental fatigue. Now I feel horribly fatigued and just awful. It's just terrible. But that's how it goes. Credit to him."
It was Federer's first reverse at SW19 since the 2016 semifinal against Milos Raonic. That one, too, went to five sets. And not since 2011 against Jo-Wilfried Tsonga had Federer fallen from two sets up in southwest London.
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Federer shut down his season due to knee problems after that loss to Raonic, and given some of the Swiss' errors Wednesday, one had to wonder if the 36-year-old was feeling something physically. Federer did take a tumble in the second set after engineering a stunning lob.
He didn't mention an injury post match but said simply that he was "average," a word not normally associated with Federer. But keep an eye on his August schedule.
"It's just not one of my best days, but they don't happen very often either," said Federer. "It's one of those average days you have to try to win the match, and I just couldn't get it done today."
The contest took place on Court 1, the first time the eight-time champion played at Wimbledon outside Centre Court since 2015 when he was in the midst of a four-and-a-half year grand slam drought.
There were no such issues for the evergreen Federer entering this Wimbledon.
He had won three of the last four grand slams he contested to lift his tally to 20 overall and was the favorite to add to that haul come Sunday evening, especially since the world No. 2 hadn't dropped a set through four rounds -- or even his serve.
The fifth-set score was reminiscent of the 2009 Wimbledon final which Federer claimed 16-14 in the final set over the unfortunate Andy Roddick. Roddick was only broken once that day.
Anderson wasn't as prolific on serve but the US Open finalist wasn't broken in the final three sets. He saved his lone break point of the fifth at 3-4 with a potent delivery and finished with 28 aces. Then Anderson broke through at 11-11, aided by a Federer double fault at 30-all.
In the past the eighth seed has sometimes struggled to close out matches but there was no issue Wednesday.
"I think the toughest thing players face when going out playing somebody like Roger in this setting is giving yourself a chance," said Anderson, who lost all eight of his previous sets against Federer. "I feel like the times that I've played him before, or other guys sort of with his ranking and history, I haven't really allowed myself to play.
"The first set was an example of that. I was really proud of myself the way I was able to relax, play my game. That's a big goal that I've had. Even if I'd lost that match in three sets or four sets, I still actually made some progress on that front.
"Obviously it's infinitely better winning that match."
Anderson will now face former college rival John Isner in what will be a battle of two of the biggest servers in tennis. Isner -- into his first grand slam semifinal -- struck 25 aces to fend off his fellow ace king, Raonic, 6-7 (5-7) 7-6 (9-7) 6-4 6-3. He hasn't been broken yet.
All this after saving two match points in the second round against Ruben Bemelmans.
Fed starts strong
When Federer broke Anderson in the first game, there were flashes of the 2014 semifinal against Raonic when he did the same. It set the tone.
Breaking for a second time to end the set in 25 minutes, no one could have forecast the drama that was to come.
"First set, felt great," said Federer. "Reading the serve. He wasn't getting many aces. When I was on, I was making him play. From the baseline I felt like I could mix it up, play aggressive.
"There was a lot going on.
"As the match went on, I couldn't surprise him any more. That's a bad feeling to have."
Anderson broke for 2-0 in the second set, becoming the first player since Tomas Berdych in last year's semifinal to take the Federer serve at Wimbledon.
But aided by a majestic defensive lob that turned into a winner in the corner, Federer broke back for 2-3 and to add to Anderson's frustration, he sent a forehand into the net on break point in the sixth game.
How costly was the fall, though? Federer didn't say.
Winning the tiebreak, Federer appeared to be on his way to victory. Holding match point at 5-4 in the third on Anderson's serve, a penetrating ground stroke from Anderson forced a backhand passing error from the top seed.
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Federer, atypically, seemed rattled. He was broken for 5-6 and failed to take advantage of 0-40 on the Anderson serve in the ensuing game. It was becoming a struggle for Federer and even more so when the Florida-based South African forced a fifth set.
Anderson capitalized at 11-11 and hung on for the biggest win of his career, becoming the fourth man to overcome a match point on the way to knocking out Federer at a major.
Nadal downed del Potro for the second time in several weeks at a grand slam, having bettered the Argentine in straight sets at the French Open en route to an 11th title.
Up a set and leading the second-set tiebreak 6-3, he was well on his way to another comfortable victory. But the injury-ravaged fifth seed recovered, assisted by a Nadal double fault on the third set point.
In the gripping fifth set, del Potro dived at volleys, slipped several times and unleashed his laser like forehand. Nadal slipped himself on consecutive points at 2-2 and at one stage went into the stands chasing a del Potro smash.
Broken for 2-3 in the fifth, del Potro subsequently missed five break chances in the next two return games. On one, with Nadal completely out of position, he mishit a forehand. The crowd groaned.
"I am very happy the way that I survived a lot of important points in that fifth set," said Nadal. "I think I did a lot of things well. I went to the net. In general terms, have been a positive match. Only negative thing is I played almost five hours, and I had the chance maybe to play less winning that second set."
Del Potro concluded the encounter on the floor again, losing his footing as Nadal put away a volley. When the 2009 US Open winner got up, Nadal was there to hug him.
"We have a lot of respect for each other. Rafa is a great champion," said del Potro.
Djokovic told Serbian media he requested a slot on Centre Court -- having played once on the main stage this fortnight -- and the three-time champ got his wish.
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Federer will have to wait until next year to return to the court he has owned.