The victory also banished memories of Dufner’s play-off defeat to Keegan Bradley in this event two years ago, when he had led by five with four holes to play.
Overnight leader Jim Furyk also bogeyed the 17th and 18th to finish two behind, with Sweden's Henrik Stenson claiming outright third on seven under to go with his runner-up finish in The Open Championship at Muirfield.
"I decided that I was going to be confident and put my best foot forward and play aggressively to try to win this thing. The last two holes were a little unfortunate but I am happy to get the job done and it's a big step in my career."
Stenson moved to within a shot of the lead with a 15 foot eagle on the fourth and was only two behind when he birdied the 13th, but he crucially bogeyed the short par four 14th after hitting his second shot from a divot into a greenside bunker.
“I’m happy with my performance,” said the 37 year old. “I think I kept it together nicely. I made a bit of a charge, made a good birdie on 13 then it was a bit unlucky that I ended up in a divot just short of the green on 14.
“I didn't play my best today but I was still hanging in there. I made a great eagle on the fourth and that kind of put me back in a good momentum again.
“I will take a lot of positives out of that. I've got a lot of big tournaments still this year, the whole FedEx Cup and the whole Final Series on The Race to Dubai, so we have got plenty of tournaments to challenge and then we have got four Majors next year.
“I’m really excited. I’m going to work hard on my game and hopefully be even better so I can even play other Sunday divots.”
Playing partner and compatriot Blixt never really threatened after dropping shots at the first two holes, but battled back to shoot 70 and claim outright fourth, one ahead of Scott Piercy and Masters Tournament champion Adam Scott.
“It was kind of exciting to be playing there, being up there with those guys and seeing your name up there,” said Blixt. “I think I've got to get used to that a little more for the next time. I can't wait to do it again.”
Furyk was aiming to follow Phil Mickelson as the second consecutive 43 year old winner of a Major and make amends for a 2012 in which he held or shared the lead after 54 holes in four tournaments and failed to win any, as well as bogeying the final two holes to lose his vital singles match to Sergio Garcia at The Ryder Cup.
Mickelson, Rory McIlroy and Ryder Cup hero Martin Kaymer were among the players who took triple-bogey sevens at the 437-yard par four, but Dufner's approach span back to within two feet of the hole for an easy birdie.