Isner, playing in his first Paris Masters final, hit 18aces – two of them during the second set tie break – which he won seven points to four.
But after staving off break points in his first two service games of the decider, the world number 27 eventually cracked when serving to stay in the match at 4-5 down.
He trailed 0-30 following his second double fault of the match. But brave net play and his 18th ace brought him parity at 30-all.
A backhand volley into the net offered up a match point for Murray and a similar error gave the second seed the prize after two hours and 18 minutes.
“I had to go for it,” said Isner after the match . “I certainly did a lot of good things out there against him and I can take satisfaction from taking him to three sets. But he was the better player in the third set. I know the scoreboard says 6-4 and it looks close. But it really wasn’t as close as that.”
Murray was presented with the L’Arbre de Fanti victory trophy by the French Olympic boxing champion Estelle Mossely.
It was an apt choice. The 29-year-old is an avid fan of the sport and he has had to fight for supremacy in the era of Roger Federer, Rafael Nadal and latterly Novak Djokovic, a troika that has ruled over the game for 13 years.
Murray will be gazetted as the 26th men’s world number one on Monday, 7 November, 2016 ending Djokovic’s 122 week stint at the top. Murray will boast parochial bragging rights as the first Briton to achieve the status since rankings were computerised in 1973.
“He has achieved the goal of getting to world number one,” added Isner. “And he is the type of guy who is going to give himself a lot of opportunities to stay there.”
Murray said after the victory that he would rethink his ambitions before the men’s end of season championships which start in London on 13 November. “We’ll sit down and look at the 2017 schedule and set goals until March. I work better with short term goals,” he conceded.
His first win at Bercy means that he has a 405 point cushion over Djokovic at the top of the rankings as they prepare for the tournament in London.
“I was not thinking of the advantage winning here would give me;” Murray said. “Having got there, it would be nice to finish the year at number one.”