Despite not managing to force a single break point in the match, Nadal won both tiebreaks, saving three set points in the first, as he won his 26th Masters 1000 title, his 59th title overall and, almost more remarkable, his ninth title of 2013.
It was not his best performance of the week - it was never likely against the giant serve of Isner, who enjoyed one of his best Masters 1000 - but, as usual, he got the job done, and he celebrated with as much delight as he has after winning any of his 12 grand slam titles.
Nadal's win will elevate him above Murray to world No.2 when the rankings are updated this morning, a significant point because he will be seeded No.2 in New York, pushing Murray down to No.3. That means that if seedings go to plan, Murray would have to beat either Djokovic or Nadal in the semi-finals and then the other in the final if he is to successfully defend the title he won so brilliantly 12 months ago.
Having won the title in Montreal eight days ago, Nadal could easily have taken things a little easier in Cincinnati and many pundits felt he would give the tournament a miss to be totally fresh for Flushing Meadows. But the Spaniard knew he was playing well and showed everyone else just how well as the supposed clay-court king maintained his unbeaten record on hard-courts this year.
It is all the more remarkable given the manner of Nadal's exit at Wimbledon, when he limped out in round one against Steve Darcis of Belgium. Few people who watched that match would have thought even Nadal could bounce back by winning Montreal and Cincinnati, played on two of the faster hard-courts on the tour.
But Nadal is not like anyone else and with no strapping on his knee and with his movement as good as ever, he romped to the title and will go into New York in arguably as good form as he was when he won his only US Open title in 2010.
"For the moment, I just want to enjoy this win," Nadal said. "I am playing very well. The US Open is one week away. To win in Montreal and Cincinnati means a lot to me. I am going to enjoy this and in a few days I will start thinking about the US Open. I hope I am ready for it."
Isner had beaten three top-10 players in Cincinnati, including world No.1 Djokovic, to reach the final and the 6ft 9in American served beautifully to keep Nadal in check.
But Nadal plays the big servers as well as anyone and even though he was sometimes returning from within touching distance of the front row in the stands, he always looked to have the mental edge. Isner had three chances to win the first set in the tiebreak, before Nadal took it 12-10, and when the second set went to a second tiebreak, the Spaniard won it more handily, 7-3, ripping a forehand down the line to clinch the title before falling on to his back and celebrating wildly.
Reaching the final will send Isner back inside the top 20 - one week after the rankings had no American men in the top 20 for the first time since their inception in 1973 - and there was no shame in losing to Nadal in this form.
"This is actually the toughest tournament in the world because the draw's smaller than a slam and everyone's in the top 50," Isner said. "I beat three top-10 guys - I couldn't beat four - but I can certainly hold my head up high after this week."
Nadal's achievements will have made Murray, Djokovic and the other contenders for the US Open sit up and take notice. Flushing Meadows is going to be fun.