After snaring the first-round lead with an opening 63 at Muirfield Village Golf Club, McIlroy notched three consecutive double bogeys en route to a six-over-par 78.
But he did not blame his dismal day on a sore left knee he tweaked during the first round, instead admitting that it was poor driving caused his high score.
"I just kept missing fairways and making it tough for myself and obviously that little three-hole stretch didn't help," the Northern Irishman told reporters on a day when Englishman Casey surged three shots clear of the field.
"Take those three holes out and it wouldn't have been that bad a day but these little runs I'm getting on it just seems to get away from me."
McIlroy was referring to the bad habit he has fallen into recently of shooting poor second rounds. In his past three PGA Tour events, he shot 77 (Masters), 76 (Wells Fargo Championship) and 74 (Players Championship) on Friday.
McIlroy arrived at Muirfield Village fresh off winning the European Tour's flagship BMW PGA Championship at Wentworth on Sunday, just days after breaking up with his tennis-playing fiancee Caroline Wozniacki.
His double-bogey run on Friday started at his fourth hole, the par-four 13th, where his second shot from the rough hit a tree and ended up even deeper in the woods.
At the par-four 14th, his approach shot from the juicy rough hit the bank of the pond protecting the green and bounced into the hazard.
Even more shockingly, he also dropped two shots at the par-five 15th, where he hit the ball twice playing a bunker shot, incurring a penalty stroke.
The resurgent Casey, on the other hand, did almost everything right to card a six-under 66 for 12-under 132, while Masters champion Bubba Watson bogeyed the final two holes to end the day in second place on nine-under.
Casey was ranked as high as third in the world in 2009, before injuries and divorce conspired to drive him to the brink of despair.
"It's very difficult when you've played to a certain level and I genuinely had no clue how to play to that level at certain stages," he told reporters.
"You start to contemplate, why am I doing this? Is there much point continuing? That's not easy. Luckily I didn't think about that too long.
"I dove into the challenge of that and that got absorbed by the process and that's the easiest way out of it because if you think too much it can become very consuming. I felt like I was on the edge of being consumed sometimes."
Casey has found his game and confidence again over the past year. He won the Irish Open on the European Tour last June and has been in solid form since.
World number one Adam Scott lamented a 70 that left him seven strokes off the pace.
"I had plenty of good golf and didn't take advantage of all my chances," he said.
Ben Rothenberg tweet: And just after Wozniacki's new Twitter picture arrived, Rory McIlroy hit three straight double bogeys (seriously). Powerful cauldron.
- Sports & Recreation
- Muirfield Village Golf Club