The match set Wimbledon semifinal records for number of games (was 72) as well as duration - the 6 hours, 36 minute match bested the previous mark by 1 hour, 52 minutes.
In the fourth set, Anderson broke Isner's serve twice to win it 6-4.
In a match full of booming serves and countless aces, the first three sets were all decided on tie-breaks.More news: Giuliani: Strzok Testimony a 'Disgrace'
The second semifinal of the day, pitting Rafael Nadal against Novak Djokovic, was easily the most highly-anticipated match of the tournament so far - and its start was delayed well over three hours as the city of London waited for either Isner or Anderson to blink. Anderson won the opening set before Isner bounced back to take the next two. He beat the defending champion 2-6, 6-7, 7-5, 6-4, 13-11 in a match that lasted over four hours.
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. The last point of the set was briefly held up as a ball boy had to be substituted after hurting his shoulder. The victor will face either Rafael Nadal or Novak Djokovic for the title on Sunday.More news: Downton Abbey movie officially a go with returning cast
Given the length of this match, it may well prove hard for Djokovic and Nadal to complete their contest on Friday.
Nadal has 17 major titles, two at the All England Club.
Isner was trying to end the longest major title drought - 58 majors - for US men in tennis history. Though Raonic outgunned Isner in that respect - 31 to 25 - he was unable to see through service games as convincingly.More news: PM announces new Canada-led training mission in Iraq