Anderson won the opening set before Isner bounced back to take the next two.
He fashioned three break points from the next rally and took the second, the first break in 49 games. While Isner's match back in 2010 was a fun side note that helped garner interest in the tournament for fans it might not usually reach, to have a never-ending saga played in the semifinal doesn't look great for the sport.
It was a similar tale in the fourth set where the South African broke for 3-2 only to hand the break straight back.
On the most crucial point of the match, Anderson recovered after a fall and hit a lefty forehand to go up 0-30 while Isner was serving at 24-24.
Nadal and Djokovic will battle for Sunday's final on the same court at 4pm.
The 31-year-old is eyeing a 13th major after making the semi-finals of a Slam for the first time since finishing runner-up at the 2016 US Open.
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