The 49th-ranked Fish followed up title success at his prior event, the grass tournament this month at Newport the week after Wimbledon.
The match win was the ninth in a row for the inspired American, who came through in just under three hours in blistering 37 Celsius conditions.
“It feels great. This is what I’ve been putting in the work for. I feel as good as I’ve ever felt in my career,” said Fish, winner of his last 10 matches and a winner of two tournaments in a year for the first time in his career.
“Playing in the heat, you have to convince yourself you feel better than the other guy, even if you’re feeling it. I struggled at the end of the match. I wasn’t used to the weather as I had played at night.
“I felt great until about 5-all in the third set, but I didn’t want to leave anything out there. I was maybe a little lucky to pull through. It was an extremely physical match with all of the heat. His no fun to play. He gives a lot of people trouble.
“My confidence is really high right now.”
Second seed Isner, winner of the longest match ever played in the sport when he won in the first round at Wimbledon, may still not have totally overcome the mental physical drain from that 11-hour contest a month ago.
Isner remains on one title this season, obtained at the start of the season in Auckland.
“Conditions were brutal again,” said Isner. “The first hour was the hottest. It took a lot out of both of us. I’ve never played in conditions this hot and humid.
“We were both just scrapping it out. This is the third final this year that I could have won. It’s disappointing – four finals this year and I’ve lost my last three.
“I know that sooner or later it will happen – I’ll make sure of that. It stinks to lose this tournament.”
The second seed was unable to put the match away after winning the first set with the break of serve which counted at the end after missing on his first five.
But Fish, playing in the faster daytime conditions which speed up the court and ball, managed to find his rhythm in the second as the heat began to war down big man Isner.
Floridian Fish profited as Isner struck a double-fault to set up a set point, which Fish grabbed to square the sets at one each.
The sixth seed went up a 3-1 break in the third set only to lose it a game later. As the last set wound into a tiebreaker Fish’s form again began to lift.
The winner over top seed Andy Roddick in the semi-finals earned a 4-1 margin, held off Isner and earned three match points as Isner hit a tired return long.
Fish advanced to victory on his second chance on a concluding unforced error from his weary opponent.
Fish lost around 15 kilograms last autumn as he recovered from knee surgery and the results has been a vast improvement in his game and fitness.
He now stands 16-2 on the ATP since the start of June after earning a finals spot on grass at Queen’s club but losing to American Sam Querrey.