The longest match ever seen on Centre Court went extraordinarily deep into the fifth set before Anderson broke Isner and served out for the win to seal a 7-6 6-7 6-7 6-4 26-24 win.
With the clock slipping past 11pm - the official curfew time for action at the All England Club to end for the day - Djokovic survived three set points in a gripping tiebreak before outlasting Nadal in a 17-stroke rally to edge ahead in the match.
A 6 hour and 35-minute battle for Greensboro native John Isner ended in defeat Friday at Wimbledon.
"It was really tough for both of us".
Update: Anderson and Isner are tied at one Set a piece.
"I think it's long overdue", Isner said.
Anderson had beaten 20-time Grand Slam champion Roger Federer to reach the semifinal against Isner.
That was played over on Court 18, which now bears a plaque commemorating the record-setter. He will take on the victor of the Djokovic-Nadal match in Sunday's final.
But there were, in fact, several breaks of serve.
Two hours and two sets in, they were even at one apiece, each via tiebreaker, with zero service breaks, only the very occasional extended point and aces by the dozen.
The American's response was immediate, breaking straight back in the next game as Anderson served for a two sets to love lead at 5-3.
In a match between two of the game's biggest servers, Anderson started the match with a double-fault. Another set point came at 9-8, but this time on Isner's serve, who saved it with a 138 miles-per-hour serve. Isner failed to convert a set point in the opener.
Anderson took the first, with Isner edging the next two to carry a 2-1 lead into the fourth set.
The American fends off another break chance at 10-10 and this insane encounter has turned into the longest Wimbledon semi-final in terms of time and the number of games, passing the insane semi-final clash between Goran Ivanisevic and Richard Krajicek that Goran won 15-13 in the fifth.
They combined for 102 aces, 53 by Isner, 49 by Anderson. The fifth set lasted 175 minutes.
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