"Playing like that in those conditions is tough on both of us", Anderson said afterwards.
Twitter was abuzz with jokes that the Anderson-Isner match could well stretch beyond the 70-68 final-set scoreline that Isner won with over Mahut eight years ago.
Anderson will certainly appreciate the chance to put his feet up ahead of Sunday's final, while Nadal and Djokovic - who have a combined 29 Grand Slam titles between them, five at Wimbledon - push each other some more.
Djokovic took the first 6-4 and the third 7-6 (9), Nadal the second 6-3.
That "endless match" prompted officials to erect a plaque on Court 18 to commemorate the feats of the two players.
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The Fox News veteran took heat online after many said he should have come to his colleague's aid rather than ask his own question. The Sun also recorded the interview and inserted audio clips into the article. "I said very good things about her".
After that, each continued to hold serve and did so for 48 games in the final set. "My left heel is killing me". "My left heel is killing me and I have an very bad blister on my right foot".
It was the longest semi-final ever played at Wimbledon, surpassing the four hours 44 minutes it took Djokovic to beat Juan Martin del Potro in 2013.
"John's such a great guy and I really feel for him because if I had been on the opposite side, I don't know how you could take that playing for so long and coming up short".
The match could not end due to a quirk of Wimbledon and two of the other Grand Slams - the fifth set cannot end in a tiebreaker.
"It's long overdue", said Isner, who suggested changing the rule to using a tiebreaker at 12-all in the fifth set.
"I personally think a sensible option would be 12-All".
Anderson defeated Isner, 7-6, -6-7, -6-7, 6-4, 26-24, after six hours and 36 minutes. John Isner of the USA reacts during his semi final match against South Africa's Kevin Anderson.
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Isner finished the tournament with a record 221 aces.
In the fifth set, Isner even jokingly asked the umpire if they could just play a tiebreak. In a fifth set that lasted 2 hours 55 minutes, Anderson never faced a break point. At 13-13 in the final set, one spectator screamed "we want to see Rafa!"
Through five wins in London, the 31-year-old has dropped just two sets and has wrapped up every match in less than three hours.
Anderson weighed in with 49 aces to reach 172 so far.
This is just the latest high point for Anderson over the course of an impressive last 11 months.
Djokovic set himself up to take the first set with strong service games, facing no break points, and broke in the seventh game before sealing it with a forehand victor.
After two-and-a-half hours of play, Anderson managed to clinch the first break of serve in the match, ending Isner's epic run of 110 straight service games won at Wimbledon.
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Anderson again broke the hard-serving American in the fourth set on his way to forcing a deciding set.