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.
It will be the second Grand Slam final for Anderson, who reached the final of the US Open previous year to Rafael Nadal.
A showdown between two tennis skyscrapers - with Isner topping the 6 foot 8 Anderson by two inches - predictably featured three tiebreaks and 102 thunderbolt aces but it was the 32-year-old South African who delivered the knockout blow.
At 24-24 Anderson took a tumble but managed to get to his feet and hit a left-handed shot inside the baseline, taking the point for 0-30.
Because of the length of the first match, that semifinal will be played with the roof closed.
Competing for the University of Georgia Bulldogs between 2003-2007 and he had an fantastic result in both singles and doubles, winning 283 matches for the Bulldogs overall!
John Isner has won the second set against Kevin Anderson 7-6 (5) to level their Wimbledon semifinal at 1-1. The last point of the set was briefly held up as a ball boy had to be substituted after hurting his shoulder. However, Melichar and Peschke won the next two games to seal it.
Nadal has 17 major titles, two at the All England Club.
The three-time Wimbledon champion posted a video to his Instagram story of him playing marbles in the dressing room as he prepares to face Nadal.
Isner was famously apart of the longest match in tennis history. Though Raonic outgunned Isner in that respect - 31 to 25 - he was unable to see through service games as convincingly.