The Northern Irish world number two battled to a seven-over-par 79 in cold, wet and windy conditions at Muirfield Village Golf Club, finishing well down the second-round leaderboard at six-over 150.
McIlroy failed to record a single birdie and wound up with two double-bogeys, one at the par-five 11th where he remarkably hit a shot backwards into water and another at the 14th, where he drove into water.
The 23-year-old covered the back nine in five-over 41 to miss the projected cut by six shots.
McIlroy had previously missed the cut at the PGA Tour's elite Players Championship earlier this month and then failed to advance at the European Tour's flagship PGA Championship in England last week.
"These two-day weeks aren't really that good for me," he told reporters on Wednesday with a broad grin, "so I just want to get some competitive rounds in.
"I'm working on a few things, and I feel trying to put them into competition will be the best way for me to prepare going into the U.S. Open."
With his U.S. Open title defence set to start at the Olympic Club outside San Francisco on June 14, McIlroy has added next week's St. Jude Championship to his playing schedule in a bid to sharpen his game for the year's second major.
