Only one match at Wimbledon lasted longer: Isner's 2010 first-round victory over Nicolas Mahut, the longest match in tennis history.
The match duration of five hours 15 minutes made it the second-longest Wimbledon semi-final after the six-hour-36-minute marathon won by Anderson against John Isner on Friday.
The fifth set alone lasted almost 3 hours as the semifinal became a test of endurance more than skill.
Novak Djokovic (SRB) celebrates match point during his match against Rafael Nadal (ESP) on day 12 at All England Lawn and Croquet Club.
Not to be outdone, Anderson had 49 aces of his own in the match. "Playing like that in those conditions is really tough on both of us", he said. "As I say the other day against Del Potro, anyone could win".
John Isner will face Kevin Anderson in the Wimbledon semifinals after the American ninth seed won the battle of the big servers against Milos Raonic on Wednesday.
Rafael Nadal believes it was an error to keep the Centre Court roof closed as he lost an epic Wimbledon semi-final to old rival Novak Djokovic on Saturday.
The second semifinal then was halted when the third set ended just past 11 p.m., because of a neighborhood curfew.
He had also gone five sets to beat eight-time champion Roger Federer in the quarter-finals, winning the decider 13-11. His US Open win a year ago was the first time he had won a Grand Slam outside of the French Open since winning the US Open in 2013.
After Isner saved a set point at 5-4 in the first with a 129 mile-per-hour second serve into the body, the match went, predictably, to a tiebreak.
Anderson, who won the fifth set 26-24, appeared to be more annoyed.
The surprise presence of Anderson and Isner means this year's Wimbledon semi-finals will feature players all over the age of 30 for the first time in the Open era.
Repeatedly, the answer was, of course, "No", even when Anderson held break points at 7-all, 10-all and 17-all.
That total was more than double the number he has had in any match against Nadal (11, on two occasions).
Yet Anderson's previously impenetrable serve suddenly looked vulnerable and in the very next game Isner broke back, once again taking the set thundering towards another tie-break. The American roared and turned to his box as he took the third set on his third set point.
In Friday's opening set, Djokovic's serve proved crucial after not faced any break points and earning the crucial break on Nadal's serve in the seventh game with a forehand victor to claim the set 6-4. You feel like this is a draw between the two of us, but somebody has to win.
Isner fell despairingly short in his bid to reach a first grand slam final at the 41st attempt.
Then, 122 minutes into the fifth set, the crowd went wild as a tired-looking Isner faced two more break points, only to save them with back-to-back aces as dark rain clouds gathered over Centre Court.
"To win against the best player in the world, the longest match I've ever played ..."