While the U.S. Open would have a 6-6 fifth set end in a tiebreaker race to win by two, with every point building in importance and drama, Wimbledon uses advantage sets and insists that you must break your opponent's service game and win the set by two games to win the match.
The No. 8 seed beat the No. 9 Isner 7-6, 6-7, 6-7, 6-4, 26-24.
It was also the second longest match at a Slam, beating the six hours and 33 minutes which Fabrice Santoro spent seeing off Arnaud Clement in the 2004 French Open.
"John is a great guy and I feel for him", Anderson told the BBC after Friday's match.
However, a semi-final of two big servers is not likely to capture the imagination much - it is unlikely to be a flashy display of tennis, but it should move quite quickly along, although let's hope we don't get into a five-setter as this is the first match on (Centre Court roof, notwithstanding).
The other was the longest match in the history of the sport, a 6-4, 3-6, 6-7, 7-6, 70-68 victory over Nicolas Mahut at Wimbledon in 2010 that lasted 11 hours, 5 minutes over three days.
But in spite of that extra time Anderson will have to recover, Isner reckons the 6ft 8in player will still struggle to match the level of physicality no matter whom he plays against.
Isner had nothing left to give, and his wait for a first Grand Slam final appearance will not come until at least the 42nd attempt, which is the record begrudgingly held by David Ferrer.
The game dragged on for a total of six hours and 36 minutes, with the final set alone taking two hours and 54 minutes.
Of course, there was another player on the other side of the net - for whom Anderson's triumph was a tragedy: Isner.
The fifth and deciding set never looked as if it was going to finish, but a break late in the day snatched victory for the South African. At 13-13 in the final set, one spectator screamed "we want to see Rafa!" They have not, however, met since 2015 in Indian Wells where Isner won in straight sets 7-6 6-2.
Reflecting on the gruelling game, Anderson called on grand slam authorities to consider changing the format of matches.
The decisive moment came in game 49 of the decider, when Anderson lifted himself off the floor, kept the point alive with a left-handed shot and went on to complete just the sixth break of the match.
"I think it's long overdue", Isner said.