From three behind Harrington might have thought a closing seven under par 64 would seal his national title for the second time in four years.
But Fisher, having lost the six stroke lead he held in the third round, responded with a 65 to take his fourth European Tour title by two.
The 29 year old's 266 aggregate, 18 under par, matched the tournament record set nine years ago by Colin Montgomerie - and with it Fisher climbs all the way from 13th to sixth in the race for places in Montgomerie's Ryder Cup Team.
"It just feels great to come out on top against such a world-class field," said Fisher after receiving the trophy and the €500,000 first prize.
"I could hear the roars and knew Padraig was making a charge. I just tried to stay patient and this is what we play for - we want to give ourselves a chance and I am no different."
Fisher could not have picked a better time to return to winning ways - the World Golf Championships - Bridgestone Invitational starts on Thursday in Akron, Ohio, and after that comes the final Major of the season, the US PGA Championship at Whistling Straits in Wisconsin.
Harrington still has not won for two years but the Dubliner, who has now had 27 second places on The European Tour, produced some spectacular shots and rated his up and down from a plugged lie in a bunker at the 12th "one of the best ever for me".
He said: "Overall I had a lot of chances. I've been comfortable with my game for a while, but I just have to trust it a little more.
"I should not get so stressed - I just have to let it happen a bit more."
Spaniard Gonzalo Fernandez-Castaño and Englishman Chris Wood shared third place on a day when there were no fewer 14 changes at the top of the leaderboard.
Wood, Australian Richard Green and Italian Francesco Molinari had an early taste of it and with four birdies in his first seven holes Harrington joined the fun.
But Fisher, round in a course record 61 on Friday, sank an 18 foot eagle putt at the seventh, holed from similar range on the ninth and then started for home with an eight iron to four feet.
That put him three clear, but it was game on again when Harrington birdied the 15th and made a ten foot eagle attempt at the 519 yard 16th.
Fisher had the same two holes to come, though, birdied them both and then to his immense relief saved par from eight feet on the next after giving his first putt far too much pace.
"Making four there was huge," he stated. "If I had come up the last only one ahead it might have been a different story."
With a closing par he could celebrate not only with his wife and one year old daughter Eve, but also with new caddie Phil Morbey on his birthday.
