A stroke behind Furyk overnight, the ultra-laidback Dufner produced some sparkling approach play as he covered the front nine in three-under 32 to reach the turn at 11 under for the tournament.
Former U.S. Open champion Furyk was alone in second after offsetting a birdie with a bogey for an outward half of even par at Oak Hill Country Club.
In-form Swede Henrik Stenson, who has posted top-three finishes in his last three starts worldwide, was in third at eight under after nine holes, two strokes better than Australia's Masters champion Adam Scott, after 10.
American Scott Piercy held the clubhouse lead at five-under 275 after piling up eight birdies and three bogeys in a closing five-under 65, while Tiger Woods ended a forgettable week with a 70 to finish halfway down the leaderboard.
However, the year's final major had been shaping up as a two-horse race for much of a sunny afternoon as Dufner and Furyk duelled for the lead.
Furyk, 43, did well to make a par four on the opening hole after finding the left rough off the tee and having to lay up well short of the green in two.
He and Dufner both parred the next two holes before Dufner sank a five-foot birdie putt at the par-five fourth to draw level at the top.
Furyk laid up in two at the fourth but hit a poor wedge approach well short of the pin and two-putted for par.
Dufner, hunting a maiden major title, briefly claimed the outright lead at 10 under after hitting a brilliant approach that spun back to two feet at the difficult par-four fifth to set up a tap-in birdie.
However, Furyk immediately rejoined Dufner at the top when he drained a slick, 35-footer to birdie the par-three sixth and both players parred the seventh, despite ending up in the left rough.
Dufner then countered with another brilliant approach, this time a sand wedge to a foot at the par-four eighth, to reclaim the outright lead at 11 under.
While Furyk bogeyed the ninth after missing the green to the right with his approach and hitting a poor chip to 15 feet, Dufner sank a clutch eight-footer to salvage par after ending up in rough off the tee and take a two-shot lead into the back nine.
(Reporting by Mark Lamport-Stokes; Editing by Frank Pingue)
