After six hours and 36 minutes, Anderson beat Isner 7-6 (6), 6-7 (5), 6-7 (9), 6-4, 26-24.
Isner then defeated Greek young gun Stefanos Tsitsipas 6-4 7-6 7-6 to reach the Wimbledon quarterfinals for the first time. Having reached the US Open final a year ago, Anderson will also be one-up on Isner in the big-stage experience department.
After being kept waiting until past 8 p.m.to start their semi-final, the duo ran out of time to finish it before the 11 p.m. curfew and will have to return on Saturday to complete the match with Djokovic leading by two sets to one. Just playing like that in those sort of conditions, just really tough on both of us.
While the Isner-Anderson marathon was taking place on Centre Court, there was another epic match being played under the radar over on Court 3. Hopefully they appreciated the battle that we faced out there against each other, but if you ask majority, I'm sure they would have preferred to see a fifth-set tie-breaker, too.
"I feel pretty awful", Isner said afterward. After losing the second set, he turned into Vintage Djoker and won 12 of the next 16 games to return to the Wimbledon semis for the seventh time.
When asked how he would recover and play in the final Sunday, Anderson said: "It's tough, I really don't know".
"I think if you ask the players, when you get stuck in these positions, playing such long matches, it's very tiring".
Their 12-year rivalry stands at 26-25 in favor of Djokovic, but those numbers don't reflect the topsy-turvy nature of the on-court relationship between the Spaniard and the Serb. "I think it's long overdue".
"I need a lot of treatment in terms of getting the body back balanced and stuff, but at the same time obviously sleep is important, too".
Anderson's win was only the first semifinal of the day.
Sporf shared a meme highlighting how Isner and Anderson spent more time playing than Germany did at the Fifa World Cup in Russian Federation.
The Djokovic-Nadal match will resume with the roof closed, a decision that was left to the players to agree upon. However many times he's lost to Djokovic in the past-and that includes the 2011 Wimbledon final-he's now No. 1 and coming off a major title in Paris, while Djokovic is still climbing his way back up the charts.
After playing his worst game of the match, Djokovic then played his best, breaking Nadal with a fabulous cross-court passing shot to get the set back on serve.
Games went with serve in the third set with Nadal failing to convert three set points in the tie-break, allowing Djokovic to take the set when his opponent netted a backhand.