Casey claimed his first victory in the United States for nine years when he edged out Tiger Woods at the Valspar Championship in March, and he will head into the final round at TPC River Highlands as firm favourite to lift more silverware.
The Englishman carded an eagle and six birdies while keeping a bogey off his card on the third day to close on 16 under, lifting him four clear of nearest challenger Russell Henley as Rory McIlroy faded out of contention after a second-straight 69 left him eight strokes adrift of his probable Ryder Cup team-mate.
Casey got off to the ideal start when he rolled in a 12-foot putt for birdie at the second and holed another from half that range at the next, and after a further gain at the eighth, he capped an outward 31 with a 20-footer for his fourth birdie of the round at nine.
The world No 13 was a whisker away from an eagle at the 13th, but he settled for a tap-in birdie before driving the green at the reachable par-four 15th and rolling in the putt from 25 feet for an eagle-two which took him three clear of the chasing pack at the time.
Casey missed a good chance to extend his advantage at 16, but he finished off his “clean” round in style as he almost spun his approach to the last back into the cup for another two at a par-four, while he also ensured that he hit all 18 greens in regulation.
The 40-year-old comfortably converted the close-range putt for his sixth birdie of the round and his best score of the season, while Henley earned a place in Sunday’s final pairing after he also went round bogey-free although he managed only three birdies in his 67.
JB Holmes holed out from 142 yards for a rare eagle at the 14th as he raced home in 30 to return a 65 and get to 11 under alongside Anirban Lahiri, who matched Holmes’ inward – and overall – score with the highlight being a stunning eagle at 13 after he drilled a 210-yard second to within a few inches of the hole.
Jason Day, already a two-time winner on the PGA Tour this year, goes into the final round with a six-shot deficit to overturn after he fired a 66 to claim a share of sixth place with double Travelers champion Bubba Watson and Memorial winner Bryson DeChambeau.
But McIlroy’s hopes of getting back into the winners’ circle look doubtful after he struggled to get going following a bizarre incident on the first tee, when he was interrupted by a squirrel just as he was about to strike his opening blow.
The roving rodent did little to help McIlroy’s focus as he carved his three-wood way right and ended up making a bogey, and he lost further ground on the leaders when his blocked tee-shot to the short fifth resulted in another dropped shot.
McIlroy did claw both shots back at the par-five sixth and 13th holes, and he then holed out from 45 feet for a thrilling eagle at 15 only to take another step backwards when he turned a great birdie chance into a bogey at the last with three putts from just outside 10 feet.
The world No 7 now needs something spectacular to deny Casey over the final 18 holes, but first-round co-leader Jordan Spieth will be playing for pride on Sunday after continuing his slide down the leaderboard with a 71, dropping shots at three of the last six holes to end the day 13 strokes behind the leader.