Eighth-seeded Anderson's prize for his bittersweet victory over his former United States college friend and rival is a date on Sunday with either world No.1 Rafael Nadal or fellow grand slam giant Novak Djokovic.
An Isner ace fittingly concluded the 12 games in the first, before Anderson recovered from a mini-break down to take a one-set lead after an hour and three minutes.
The marathon tie meant that the Nadal v Djokovic semi-final was to be played under the roof as the light began to fade just after 8pm.
Anderson finished with 49 aces and 118 winners; Isner had 53 aces and 129 winners.
Each player held his next serve before Anderson broke Isner again to go up 5-4 and then proceeded to serve out the set to send the match to a decisive fifth set.
This put the 32-year-old Anderson in a good spot as Federer was not playing on his favourite Centre Court. 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.
Anderson had a break and set point chance at 5-4, but Isner fired down a gutsy 129mph unreturned second serve to keep himself in contention.
Those named Kevin Anderson are being offered a free "victory feast" for them and two friends - in honour of his three-set victory. It was a drama filled set that went back-and-forth, similar to the third set.
It's his second showpiece appearance in four major tournaments after his runner-up finish in last year's US Open. He made it 0-30 in that game by winning a point after falling on his back behind the baseline but still got up in time to return Isner's shot.
Nadal and Djokovic will meet for the 52nd time. For us to be out there for that length of time.