McIlroy shot an even-par 71 at Royal County Down, but his opening-round 80 proved too difficult to overcome. At 9 over, he was four shots outside the projected cut line and will miss the cut for the second consecutive week.
"I left myself too much to do from yesterday," McIlroy told reporters after the round. "I played a solid round of golf today, but it just wasn't enough."
McIlroy was unable to convert on several early scoring opportunities, and he did not record his first birdie of the week until the seventh hole of his second round. He added another birdie on No. 12 to get to 7 over and within reach of the cut line, but a double bogey on No. 15 ended his chances of playing the weekend. His tee shot on the final hole found a gorse bush, but McIlroy scrambled to save par, giving the fans one last reason to cheer.
The world No. 1 was coming off a missed cut in defense of his title at the BMW PGA Championship, and he has now missed the cut at the Irish Open for the third consecutive year - across three different courses.
"The support out here is phenomenal, but this is going to be the third year in a row that they won't see me playing at the weekend," McIlroy said. "It's disappointing, to say the least."
While McIlroy could still add another event to his schedule, this is expected to be his final competitive appearance before the U.S. Open. Since 1997, the only player to win the U.S. Open after missing two consecutive cuts was Webb Simpson at the Olympic Club in 2012.
McIlroy was not the only big name to struggle this week at Royal County Down. Sergio Garcia missed the cut after rounds of 75 and 79, while Victor Dubuisson carded a 13-over 84 in the second round. Martin Kaymer, McIlroy's playing partner, is also expected to miss the cut at 6 over.