Despite going on for almost seven hours, Isner was nowhere close to beating his own record for the longest tennis match history - a first-round victory over Nicolas Mahut, which went on for more than 11 hours over three days and finished 70-68 in the fifth in 2010 also at Wimbledon.
"It's a match that's often won on just a couple points here and there".
With years of familiarity between them and scant difference in their towering height and ballistics serves, Isner and Anderson traded blasts for hours without either asserting dominance.
Isner, 33, a native of Greensboro, N.C., and Anderson, 32, who was reared in Johannesburg, were longtime rivals at the top ranks of college tennis, when Isner played for Georgia and Anderson, for IL.
Anderson had a break and set point chance at 5-4, but Isner fired down a gutsy 129mph unreturned second serve to keep himself in contention. Though Raonic outgunned Isner in that respect - 31 to 25 - he was unable to see through service games as convincingly. Djokovic owns 12 Slam trophies, three from Wimbledon. That game is commemorated with a plaque on Court 18.
Isner has won eight of the 11 professional matches against Anderson and is projected by many to advance from this battle of two of the game's biggest servers.
After taking a medical timeout after the third set, Anderson surprisingly broke Isner's serve at 2-all in the fourth. The third-set tiebreak was a compelling match-within-the-match, featuring blistering passing shots and deft volleys.
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.
With fellow semi-finalists Rafael Nadal and Novak Djokovic waiting in the wings, Isner and Anderson made the most of their first appearance on Centre Court in these championships - staying on court for six hours.