McIlroy came into the event as the pre-tournament favourite on the back of top-five finishes in his last two starts and a brilliant record at the host venue Quail Hollow.
The 28-year-old won his first PGA Tour title here in 2010, lost out to Rickie Fowler in a play-off in 2012 and stormed to a seven-shot victory in 2015, which included a course record of 61 in round three.
However, changes to several holes and the installation of bermuda rough and greens had not suited the four-time major winner, who struggled to consecutive rounds of 72 to lie 10 shots off the lead at halfway.
No player has ever won the final major of the year after trailing by more than nine strokes after 36 holes and McIlroy, whose last major win was the 2014 US PGA, looked incapable of bucking that trend, starting round three with bogeys on the second and fifth.
The same could also be said of Open champion Jordan Spieth, who had already admitted his bid to become the youngest winner of the career grand slam was effectively over.
”I kind of accept the fact that I’m essentially out of this tournament pending some form of crazy stuff the next couple of days,” Spieth said. ”I’m sure going to give it a try.”
Spieth began his third round 11 shots off the lead and dropped shots at the first, fourth and seventh before repairing most of the damage with birdies on the eighth and ninth.
That still left the 24-year-old 12 strokes behind halfway leaders Kevin Kisner and Hideki Matsuyama, whose second round of 64 had established a course record for the new layout, just five days after he equalled the course record of 61 at Firestone Country Club to win the WGC-Bridgestone Invitational.
Former world number one Jason Day and American Chris Stroud were two shots off the lead, Stroud one of 25 players to complete their second rounds on Saturday morning after Friday’s weather delay.
For the second successive major the cut fell at five over par, with 75 players qualifying for the final two rounds.
Austria’s Bernd Wiesberger would have made the cut four over par with a birdie on his final hole, but bogeyed it instead to miss out by a shot and end his streak of 26 consecutive events earning world ranking points.