As Isner served for a 16-15 lead, the match became the second-longest Wimbledon singles clash at just over five and a half hours.
John Isner was one win away from his first career Grand Slam title.
The South African needed six hours and 36 minutes to see off Isner 7-6 (8-6) 6-7 (5-7) 6-7 (9-11) 6-4 26-24 in a truly epic encounter featuring 102 aces and 96 service games.
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.
Those named Kevin Anderson are being offered a free "victory feast" for them and two friends - in honour of his three-set victory.
When their semi-final ticked past the five-hour 31-minute mark, it beat the previous mark set by Marin Cilic and Sam Querrey in the third round in 2012.More news: Reds set to sign Xherdan Shaqiri by this weekend
More news: Chris Weakens to Tropical Storm, Island Braces for Heavy Rain Tonight
More news: President Donald Trump to visit Windsor on United Kingdom tour
The first match on the Tour between these two was in Las Vegas in 2008 but they have played a very important match in Collegiate tennis back in 2007, and this is a nice occasion to go back in past and examine their Collegiate careers.
Anderson had beaten 20-time Grand Slam champion Roger Federer to reach the semifinal against Isner.
The 32-year-old Anderson will vie for the title on Sunday against the victor of the match between Nadal, the world No. 1, and three-time champion Novak Djokovic.
Given the length of this match, it may well prove hard for Djokovic and Nadal to complete their contest on Friday.
The other men's semifinal features two big servers bidding for a first major championship: Kevin Anderson of South Africa and John Isner of the U.S.