The match is likely to re-open the debate about allowing tie-breakers in the final set at Wimbledon.
In a matchup of two of the tallest (Isner at 6 feet, 10 inches, Anderson at 6-8) and biggest-serving players on the ATP tour, Isner and Anderson expectedly played tiebreaks in each of the first three sets.
At six hours and 35 minutes, it was the longest match ever played on Centre Court and the second-longest match at The All England Club.
The Canadian and partner Yifan Xu of China, seeded sixth, lost 6-3, 4-6, 7-5 to No. 12 seeds Nicole Melichar of the USA, and Kveta Peschke of the Czech Republic in the Wimbledon semifinals on Friday.
Neither Isner nor Anderson had won a Grand Slam title nor, prior to this week, advanced beyond Wimbledon's fourth round despite a decade of trying. Because of the length of the first match, that semifinal will be played with the roof closed. The two went back and forth all the way to 12-all, essentially playing a full sixth and seventh set.
Isner did, however, break the record of the most serves at a tournament - beating Goran Ivanisevic's 213 on his way to the Wimbledon back in 2001.
It is common to hear the call of 15-all in tennis, but, in this instance, that was the score in games at one stage in the fifth set as both players continued to resolutely hold serve.
"I don´t really know what to say right now, playing like that in those conditions was really tough for the both of us", said eighth seed Anderson. Isner and Anderson have played each other before professionally and they were rivals in college (Isner, 33, played at the University of Georgia, and Anderson, 32, at University of Illinois). Isner won that best-of-three match 7-6, 6-1.
After taking out Roger Federer in remarkable fashion, 2017 US Open runner-up Anderson was forced to go the distance once again and he triumphed in remarkable fashion.