The 6Ã¢â‚¬â„¢9Ã¢â‚¬Â American could have been a basketball player and he may have been wishing he had chosen a different court of battle as Murray demolished him with a virtually flawless performance in front of the Rod Laver Arena crowd.
Murray executed his game plan to perfection, playing aggressive tennis from the outset and never allowing Isner to find a rhythm or gain consistent control of the points. The Brit also matched uncompromising attack with superb consistency, allowing just eight unforced errors off his racquet in 132 minutes on court.
The Murray camp had clearly done their homework ahead of the pairÃ¢â‚¬â„¢s first meeting, with the Scot choosing to take some pace off his first serve to ensure he got a high percentage in court. The second serve, which has been picked out as one of his few weaknesses, was, by contrast, heavier and more accurate.
Murray backed that up with constant pressure on the Isner serve. It was a measure of just how well Murray returned throughout the match that the American managed to fire down just 14 aces compared to the 27 he averaged in the previous three rounds.
The number five seed took a tight first set which could have gone either way. He probed at IsnerÃ¢â‚¬â„¢s serve throughout but the AmericanÃ¢â‚¬â„¢s big weapon his came to his aid whenever Murray created a chance for himself.
It was against the run of play that Isner created a set point at 5-6 on the Murray serve, but the Scot responded with a brave second serve to level the score once more.
The pair exchanged minibreaks early in the tiebreak before Isner double faulted at 3-4. The error proved decisive as Murray turned up the pressure and went on to win the breaker.
It was after an hour and 34 minutes that the number five seed finally made the first breakthrough. He created three break points courtesy of a huge forehand down the line and put in a cleverly angled second serve return to eventually force the error from his opponent and clinch a 5-3 lead.
The American responded by creating couple of break points of his own but Murray snuffed out the danger with more great serving to secure a two-set advantage.
From there, the Brit went from strength to strength. At 2-2 in the third, he set up three break points with arguably the shot of the tournament so far. Isner hit what he thought was a smash winner, only for Murray, with his back virtually against the hoardings, to slam a backhand at IsnerÃ¢â‚¬â„¢s feet.
The Scot then followed it up with a sensational running backhand pass to claim his second break of the match. He reeled off the next three games in quick succession as IsnerÃ¢â‚¬â„¢s game thoroughly broke down under the intense pressure from Murray.
He will face Rafael Nadal in the quarter-final, who beat Ivo Karlovic 6-4 4-6 6-4 6-4 in the second match on Rod Laver.
MORE: The latest football news
MORE: The latest tennis news
BIOGRAPHY: Nemanja Matic
BIOGRAPHY: Jesse Lingard