Anderson defeated Isner in the fifth set 7-6, 6-7, 6-7, 6-4, 26-24.
Isner also took part in the longest match - period, no caveats - in tennis history, which, astoundingly, almost doubled the duration of Friday's contest.
The 6-foot-10 Isner finally succumbed to the 6-foot-8 Anderson just before 8 p.m. local time in a grueling encounter full of plot twists in the longest men's semifinal in Wimbledon history.
Spectators cheers as Kevin Anderson reacts after defeating John Isner 26-24 in the final set of their semi-final match at Wimbledon Friday.
The lefty shot would prove critical as Anderson would win that game to break Isner and then serve out the match.
Kveta Peschke, 43, and her American partner Nicole Melichar advanced with a 6-3, 4-6, 7-5 victory over Gabriela Dabrowski and Yifan Xu. "I personally think a sensible option would be 12-All", said Isner who was bidding to reach his first Slam final at the 41st attempt. They combined for 102 aces: 53 by Isner, 49 by Anderson.More news: Conte out at Chelsea
The victor of Rafael Nadal vs Novak Djokovic awaits Anderson in Sunday's final. There was the deluge of aces (more than 100, in fact), the three tiebreakers, the final set that itself lasted almost three hours. The fifth set lasted 175 minutes.
That is perhaps a surprise considering Anderson is the more complete player.
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.
The match was ironically labelled "pointless" by viewers who complained Anderson would be left worn out for Sunday's final.
The 33-year-old agreed with Anderson that all Slams should introduce a tiebreak in the final set and fall in line with the US Open.
And repeatedly, the answer was, of course, "No", even when Anderson smacked a return victor at Isner's feet to get to break point at 7-all, 30-40. The Spaniard converted two out of three opportunities to break serve in the second set. "I felt like I did some good business here in the past already", he said.
Quotable: "I like the level of tennis that I'm playing on right now".