Murray, winning for the first time in the French capital, claimed his 14th Masters title and third of the season. A late-season charge has seen him win four straight tournaments in a 19-match unbeaten run to usurp Novak Djokovic at the top of the standings.
"This has been an incredible journey for me to get to the top of the rankings," he said at the trophy presentation.
Isner, who produced some of his best tennis as he leveled at one set all and forced a decider, also paid his tribute.
"I have to congratulate Andy -- to get to No. 1 in the world that's an incredible achievement," the American said.
"Every week I see you in the same locker room and see how hard you work."
Isner certainly made Murray work hard after dropping the opening set to a single break and kept producing big serves in the second to force a tiebreak.
He took it with inspired play, but Murray kept his patience and when Isner had a temporary lapse when serving at 4-5 down in the decider he pounced to ruthless effect.
He now faces a showdown with defending champion Djokovic in the ATP Tour Finals in London from Sunday week, with the end of year No.1 ranking on the line as well as pride.
Murray, who has not gone past the semifinals in the prestigious eight-man event, is determined to put that right in front of his home fans.
"I'm not so much thinking of finishing the year as world No. 1 I just want to play well and do myself justice," he told Sky Sports.
It will be a family affair at the 02 Arena, with his brother Jamie and partner Bruno Soares going into the tournament as the second-ranked doubles pair.