It was, inevitably, a match of big serves galore, with an 129mph second serve from Isner a highlight, but both offered plenty off the ground too in an engaging five-set encounter.
And he made it clear Grand Slam tournament organisers should consider a rule change - perhaps introducing a tie-break at 6-6 - to make the deciding set of five-set matches less gruelling.
For much of the afternoon on the All England Lawn Tennis Club's centre court - which eventually stretched to an incredible six hours and 35 minutes - proceedings went according to the script.
However, Isner was then unable to convert a set point of his own in the tiebreak before 32-year-old Anderson wrapped it up thanks to a netted return.
Roanic had only been broken three times this Wimbledon previously but Isner doubled that tally alone to triumph 6-7, 7-6, 6-4, 6-3.
"In the matches I've played him, obviously taking care of your serve is the first priority".
While the match was tense, it was far from compelling, with both power players simply blasting serves past one another and trading service in the final set.
He also broke the record for most aces in a Wimbledon tournament.
Isner and Anderson were no strangers to each other, facing off all the way back to their college days, when Isner defeated Anderson, who played at IL, in the 2007 NCAA Men's Team Final.
The reason the match went on for so long comes down to one of Wimbledon's quirks - a five-set match can not end on a tiebreaker, a tradition shared at the French Open and the Australian Open.
Isner's semifinal match is scheduled for 7 am Dallas time on Friday and can be watched on ESPN.