Murray cruised to a 6-1, 6-3 win over the big American who required treatment on his blistered right hand early in the second set.
Murray, the 2014 champion in the Austrian capital, cruised to a 6-1, 6-3 win over the big American who required treatment on his blistered right hand early in the second set.
World number two Murray, who now has 68 wins in 2016 and is on a 14-match win streak, broke serve three times in a dominant opening set, committing just one unforced error to Isner's 20.
By the end of the one-sided affair, Murray's error count was just 10 to 35 to the outclassed American.
Murray needs to win the Vienna title on Sunday, as well as next week's Paris Masters, to have a chance to knock Djokovic off the world top spot.
On Saturday, the 29-year-old faces defending champion and fifth seed David Ferrer who saved a match point and recovered from a break down to beat Serbia's Viktor Troicki 6-3, 3-6, 7-5.
Ferrer, who is attempting to extend a streak which has seen him reach at least one final in each of the past 11 years, will be up against it facing Murray -- he trails 6-14 with the Scot winning the last seven.
Big-serving Ivo Karlovic saved a match point and fired 29 aces to defeat Russia's Karen Khachanov 6-7 (5/7), 7-6 (7/5), 6-3 to reach the semi-finals.
Karlovic, 17 years older than his 20-year-old opponent, saved the match point in the 12th game of the second set.
The Croatian veteran will next face sixth seed and 2011 champion Jo-Wilfried Tsonga of France who defeated Spain's Albert Ramos-Vinolas 6-2, 7-6 (7/5).
Karlovic now has a season-leading 1,081 aces.