The Northern Irish world number two struggled to a three-over-par 73 in Friday's second round to finish at 10-over 150, two strokes off the cutline.
"Obviously I'm disappointed. It wasn't the way I wanted to play," McIlroy said after racking up five bogeys and just two birdies in fast-running conditions on a sun-drenched afternoon.
"I left myself with a lot of work to do after yesterday's round, and to be honest overall I don't feel like I played that badly for the last two days."
McIlroy, who last year at the age of 22 became the US Open's youngest winner since 1923, had opened with a 77 after hitting only seven of Olympic's 14 twisting fairways.
"It's just such a demanding golf course and punishes the slightest shot that's offline or that's maybe not the right distance or whatever," the mop-haired McIlroy said.
"You really have to be so precise out there and if you're not, you're going to get punished. We're just not used to playing this sort of golf course week-in, week-out.
"We're not used to having to land balls before the edge of the greens to let them run on. It's just something that you have to adjust to in this tournament. I wasn't able to do that very well this week."
McIlroy became the first defending champion to miss a US Open cut since Argentina's Angel Cabrera at Torrey Pines in 2008. It was also the fourth time he had failed to advance to the weekend in his last five events worldwide.
"You just got to keep working hard," said McIlroy, who won his third US PGA Tour title at the Honda Classic in March. "It doesn't come easy to you all the time yeah.
"It hasn't been the greatest run over the last six weeks or whatever it is, but I still see enough good stuff in the rounds that it does give me hope that it's not very far away."
McIlroy, who had teed off for the second round from the par-four ninth, suffered a frustrating finish.
He drove the green at the 288-yard seventh but had to settle for a birdie after his eagle putt from 25 feet ran past the cup.
At the par-three eighth, his tee shot settled just 15 feet short of the flagstick, leaving him with a tricky birdie putt that would have saw him make the cut. But he missed then three-putted for a bogey.
"Once I missed that, I knew that I probably wouldn't make it through the weekend," McIlroy said.
"But I felt like I had some good shots out there and I don't think the score that's on the board really reflects how I played."