McIlroy had begun the day a shot behind Xander Schauffele and trailed him by two strokes after the American made an eagle on the seventh.
But from then on the world number two was sensational as he left Schauffele in his trail, playing the next eight holes at eight-under, including a pair of eagles.
"I just went on a run that, for whatever reason, I'm able to go on with this golf course," said McIlroy after his fourth win at Quail Hollow, where he enjoyed the first of his 26 PGA Tour victories as a 20-year-old back in 2010.
The round was only slightly blemished by a double bogey on the 18th, where he found the water beyond the green but the Northern Irishman's total was still the lowest round of the day.
After his win at the Zurich Classic of New Orleans team event last month, with Shane Lowry, McIlroy now heads into the second major of the season, the PGA Championship at Valhalla with back-to-back wins.
McIlroy has not won a major since capturing his fourth at Valhalla 10 years ago but he is now in buoyant mood.
"My golf swing feels a lot more comfortable than it has done, so going to the venue next week where I've won, it feels like the stars are aligning a little bit," said the 35-year-old.
"But I've got a lot of golf to play and a lot of great players to try to beat next week but I'm going into the next major of the year feeling really good about myself," he added.
He had begun his round with a birdie on the opening hole and followed it up with another on the fourth but there was little sign of what was to come.
After Schauffele made a tricky 12-foot downhill putt on the par-5 seventh for eagle, McIlroy missed his 10-footer for birdie and fell two behind.
Schauffele must have felt that was a potential momentum shift in their tight battle and it proved to be - but not in the way the American hoped.
McIlroy birdied the next two holes, while Schauffele could only make par and then on the tenth the Northern Irishman's brilliant 34-foot putt earned him an eagle.
Schauffele missed his eagle putt, losing his lead with a birdie and it was an advantage he was never to regain as he bogeyed at 12, 13 and 16.
McIlroy turned the screw with birdies at the 13th and 14th before the decisive blow came with an eagle on the 15th, holing out from the greenside bunker with a sublime shot of extreme control to grab a six-shot lead.
Schauffele ended with an even-par 71 and while he may later reflect on a positive week, he accepted that McIlroy had simply been unstoppable.
"I mean, he played unbelievable. Looked up at the board and I'm like dang, he's 6 under through 6 on the back nine, it's something else," he said.
"When you take a step back, yeah. He's Rory McIlroy, you know? He hits it 350 yards in the air downwind and he has shorter clubs into firm greens than anyone else. When he's on, he's on. Hats off to him," he added.
South Korea's An Byeong-Hun finished third after a fine, six-under 66 left him three shots off Schauffele.
Australia’s Jason Day and South Korean Im Sung-Jae were tied for fourth, both on six-under.
