Meanwhile, Anderson and Isner called for Grand Slam chiefs to introduce a cut-off point for final set marathons.
From the way Novak Djokovic repeatedly smacked his racket against his shoe after one miss, to the shouts directed at himself and his coach after others, it was clear how much he wanted to prove he's past the roughest patch of his career.
The 6-foot-10 Isner finally succumbed to the 6-foot-8 Anderson just before 8 p.m. local time in a grueling encounter full of plot twists in the longest men's semifinal in Wimbledon history. Anderson won the fifth set, 26-24. But serving in the fourth, Isner got a shock break, however Anderson would give it right bad.
Having once again swapped breaks early on in the fourth set, Anderson broke Isner for the third time, and took the match into a decider on his fourth set point.
"It's true that the schedule was a little bit tight knowing that the first match was between two big servers", said the 32-year-old.
The result came two days after Anderson stunned eight-time champion Roger Federer in four hours and five more sets, saving a match point in the process.
"I was for the roof because we started to play, and I wanted to play in the same conditions". "For us to be out there for this length of time - I mean not just on us coming back, trying to compete at this sort of stage, going through this - It's happened to John before, when he has played another five hours".
With Djokovic hitting the lines with relentless regularity, Nadal saved two more break points at 1-1 then seized the initiative to punish Djokovic for his first lapse. "I think it´s long overdue".
"You know, a few days' rest, maybe more than that, and I'll recoup an Isner said that being part of yet another record-breaking match did not help ease his pain".
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Nadal and Djokovic regularly - and spectacularly - ran down shots to force long rallies, drawing gasps and cheers from the appreciative crowd.
Wimbledon fans witnessed history as the longest semi-final ever at the Championships unfolded on Centre Court.
Anderson reached his first grand slam final at the US Open a year ago, at the 34th time of trying. "I'm not going to change that now", said the American.
"It's fair to say that was a great match and he beat me".
Isner fell despairingly short in his bid to reach a first grand slam final at the 41st attempt.
He had break points in the 15th, 21st and 35th games of the decider before taking victory when a tired Isner, who had needed treatment for blisters on his right hand, hit long."It just seems cruel and unusual punishment for these guys", former champion John McEnroe said on the BBC. "I think it needs to be done".
How he does that after contesting the longest ever Grand Slam semi-final is anyone's guess. With how I'm feeling physically and mentally, I'm in a very good spot.
In Friday's opening set, Djokovic's serve proved crucial after not faced any break points and earning the crucial break on Nadal's serve in the seventh game with a forehand victor to claim the set 6-4.