Unbeaten on the surface in 15 matches this year and coming off a win in Montreal, the third ranked Nadal, who will move up to number two on Monday, won back-to-back hardcourt finals on consecutive weeks for the first time in his career.
"It means a lot, being able to win two straight titles, two Masters 1000 on hard back-to-back is just amazing for me," Nadal told reporters. "I never did something like this in all my career, so it was an emotional moment for so many different reasons.
"It is a nice feeling to arrive to the U.S. Open with two victories in two very difficult tournaments.
"And it is nice arrive there knowing that, if I am able to keep playing like this, hopefully, I have the chance to have a good result."
Nadal needed nearly two hours on a muggy centre court to tame the towering in-form American, who had knocked off three top 10 players, including world number one Novak Djokovic, to earn his spot in the final.
But the big-hitting Isner had no answers for the relentless Nadal, who has now claimed nine titles from 12 events this season.
It was the 59th win of Nadal's career but first in nine tries on the Cincinnati hardcourts.
Isner, who has traditionally saved his best for the home crowd with 14 of the his 16 career ATP Tour final appearances coming in the U.S., had the capacity crowd in his corner and bombarded Nadal with 11 aces but could not crack the Spaniard's defences failing to convert any of three break chances.
Nadal played the entire match without a single break opportunity against Isner but came up big in both tiebreaks taking the first set 10-8.
Eager to avoid a third set against the determined Isner, the 12-time grand slam winner was even more aggressive in the second set tiebreak racing to a 6-3 advantage then falling onto his back and leaping into the air when the American's return slammed into the net.
"He kept on coming up with the goods," shrugged Isner. "I thought he played a very smart match, and I knew he would.
"That's what he does. That's why he's so good. He's constantly adjusting to every circumstance, and he did today with me."
Isner, who will move from 22 to 14 in the world when the new rankings come out, has also established himself as a legitimate threat when the final grand slam of the season gets underway in Flushing Meadows on August 26.
Since retiring in the second round at Wimbledon with a left knee injury Isner has been in brilliant hardcourt form putting together a 16-4 match record while picking up his seventh career title in Atlanta followed by runnerup finishes in Washington and Cincinnati.
"I would say Rafa is the favourite going to the U.S. Clear cut? I wouldn't say that," said Isner. "I think he'd probably say the same."
