Dufner, 36, had shared the 54-hole lead at the 2011 PGA in Atlanta and had a five-shot lead with four holes to play only to lose a play-off to Keegan Bradley, and he was defending a two-stroke lead with the tough finish to play, although his nearest rivals were failing to make inroads over the closing holes.
McIlroy, 24, had put himself in with a chance of victory with a third-round, three-under-par 67 on Saturday that left him on three under for the week, six shots behind 54-hole leader Jim Furyk at the start of yesterday's play.
The two-tie major winner, a year on from his record eight-shot PGA win at Kiawah Island, got off to a hot start in upstate New York when he sunk a long birdie putt at the par-three third and then lasered in his approach to the par-five fourth to inside four feet.
The world number three missed the opportunity to close the gap further though, but it was a cruel bounce at the next hole which really ended his chances of mounting a serious challenge. Playing the par-four fifth hole, McIlroy was nicely positioned on the fairway off the tee and looking set to give himself another birdie chance when his approach into the green found the downhill slope and rolled off the putting surface onto the rocks beside greenside creek.
And it got worse from there, the Irish star, having taken a penalty stroke, sending his fourth shot from the drop zone over the green and into thick rough on his way to a victory-snuffing triple-bogey seven that sent McIlroy reeling back to one under, eight shots off the lead.
McIlroy was rallying, with birdies at the par-four ninth and 10th to return to level par for the round and added another birdie at the par-five 13th to move back to four under, only to give that shot right back with a bogey at the par-four 16th, having missed the fairway off the tee and failed to get back on with his second shot. With two to play, the best he could hope for was a best finish in the majors this year, something he was comfortably achieving as he closed in on a top-10 finish.
As McIlroy's hopes faded early, 54-hole leader Jim Furyk and Dufner were busy making birdies, reducing the potential contenders to a handful of golfers.
Playing together in the final group, Dufner held a two-shot lead over the 43-year-old Furyk as the pair turned for home, the latter having bogeyed the ninth after missing a 15-foot putt, the former sinking his par putt from around 10.
And with four to play, Dufner was still out front on his own on 11 under par, with Furyk on nine under, a shot ahead of Sweden's Henrik Stenson, whose playing partner in the penultimate group, compatriot Jonas Blixt was on seven under with three to play.
Dufner, who followed up his course-record 63 on Friday with a one-over 71 on Saturday, had started a shot behind 2003 US Open champion Furyk on eight under before overtaking the 54-hole leader with back-to-back birdies on the fourth and fifth. Furyk joined him on 10 under when he birdied the par-three sixth, only for Dufner to birdie the eighth before the veteran slipped up at the ninth.
Masters champion Adam Scott was one under for his final round on a six under for the tournament after 16 holes with American Scott Piercy holding the clubhouse lead on five under following a closing 65.
Also in the clubhouse were Graeme McDowell, whose four-under-par 66 was his best round of the week and indeed of any major this year, looking set to give the Portrush man a top-15 finish. McDowell was on two under, alongside Boo Weekley, who shot a 67 and Marc Leishman (68).
Tiger Woods will have to wait another year for his return to the winner's enclosure in a major after a closing-round level-par 70 kept him pegged at four over par for the tournament.
“I was close in two of them,” Woods said “I was right there and certainly had a chance to win the Masters and the British this year. The other two, I just didn’t hit it good enough. Just the way it goes.
“Having a chance on the back nine on Sunday, I can live with that. It's always frustrating going out there, and I'm three over today, got to 7, and I'm grinding my tail off coming in just to shoot even par for the day. And I'm nowhere in it. That's tough.”