Djokovic won that meeting in five sets, 7-5, 4-6, 7-6, 6-7, 6-3.
Anderson is 0-5 in his career against Nadal, with his last bout coming in a three-set loss at the 2017 U.S. Open. Isner wasted a set point in the opener.
But his record in fifth sets slumped to 9-18 overall, including defeats of 19-17, 18-16, 12-10 and now 26-24.
"I'm a proponent of changing that rule, for sure", Isner said. "I've hit a lot of left-handed balls throughout my life". My left heel is killing and I have an terrible blister on my right foot.
The previous longest semifinal match at Wimbledon was in 2013, when Djokovic beat Juan Martín del Potro in 4 hours, 44 minutes.
When asked how he would recover and play in the final Sunday, Anderson said: "It's tough, I really don't know". The 50-game final set took about three hours alone. He criticized the lack of a deciding-set tiebreaker at Wimbledon, the Australian Open and the French Open.
Additionally, Anderson called for a change in the tournament format so that players won't have to go through such long matches. "I think he will expect that, as well".
Isner, the ninth-seeded American and Anderson, the eighth-seeded South African, are both power servers who struggle with their returns. Anderson then took the fourth set 6-4, breaking the Isner serve twice in the set.
It was the kind of ingeniousness that was needed to break the serve-hold-serve-hold deadlock that went on for nearly three hours in the deciding set alone as Anderson became the first South African man in 97 years to reach the Wimbledon final.
The crowd knew it, the spectators knew and although Isner might not be willing to admit it, Anderson did.
Numerous best points came in the tiebreaker, including a 23-shot rally that Nadal finished off with a forehand half-volley drop shot to set up his first set point. This time, Anderson served out the set, avoiding a tiebreaker. The American roared and turned to his box as he took the third set on his third set point. All Anderson did was eliminate Roger Federer in the quarterfinals, erasing a match point and a two-set deficit.
Back and fully healthy, Djokovic and Nadal should give us a match to see.
A showdown between two tennis skyscrapers - with Isner topping the 6 foot 8 Anderson by two inches - predictably featured three tiebreaks.
In addition to his own 161 aces, the 208cm-tall Isner has won every single one of his 95 service games, facing a measly seven break points in five matches. Because it was so late, and with rain forecast, the All England Club shut the retractable roof above the main stadium before the second semifinal.
At one point in the fifth set, a spectator shouted, "Come on, guys!" Anderson finally came through on his sixth for a 25-24 lead, when Isner wearily put a backhand into the net.