Djokovic holds a 2-1 lead in sets after claiming the third-set tiebreaker, 6-4, 3-6, 7-6 (9).
The match will finish on Saturday.
"It's a bit of a sign for the grand slams to change this five-set format", he said. Not only is he advancing to the first Grand Slam semifinal of his career at Wimbledon, he and his wife, Highland Park native Madison McKinley, are expecting their first baby girl.
The result came two days after Anderson stunned eight-time champion Roger Federer in four hours and five more sets, saving a match point in the process.
"It was really tough for both of us".
Isner previously won the longest ever Grand Slam singles match against Nicolas Mahut, lasting 11 hours and five minutes over three days in the 2010 Wimbledon first round.
"That definitely brings a smile to my face", said Anderson, the runner-up to Nadal at last year's U.S. Open.
"I agree with Kevin". In the fourth set, the American seemed to tire, with Anderson surging to a more conventional 6-4 win and seemingly ready to wrap it up. "I think it needs to be done".
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.
But that break in the eighth game of the third set did not hurt anything like the moment when he finally slapped a tired forehand wide at 7.46pm local time to surrender his title hopes. "I just put the racquet in my left hand and managed to hit a pretty decent shot".
"We've been lined up against each other for about 14 years now, because he left IL when I left Georgia".
"So, I apologise if I'm not more excited right now.so many mixed emotions in getting through something like that". The record, funnily enough, was set by Isner.
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"That's no consolation to me".
"I'm a proponent of changing that rule, for sure".
There are zero major titles so far for either Isner, 33, or Anderson, 32, who shockingly ended Federer's bid for a ninth championship at Wimbledon by erasing a match point and beating him 13-11 in the fifth set of their quarterfinal Wednesday. The victor of the match will face off against the victor of John Isner and Kevin Anderson.
He had break points in the 15th, 21st and 35th games of the decider before taking victory when a tired Isner, who had needed treatment for blisters on his right hand, hit long. John is such a great guy.
The only silver lining for Anderson, if it can be called that, is that the length of his match had a knock-on effect on the Nadal-Djokovic semi-final.
The pressure continued to mount on the world No. 1 as Djokovic created another break point opportunity, with his Spanish opponent punching the air with glee after denying the Serb.
Nadal and Djokovic, meanwhile, are in the midst of their 52nd meeting, with Djokovic holding the edge 26-25.
Djokovic retired in that match because of a toe blister.
Some did see the amusing side, providing some alternative statistics to what was officially the longest ever Wimbledon semi-final.
Djokovic, meanwhile, is seeking a fifth final at the All England Club and 22nd at the Slams.