McIlroy ended a torrid two days at Royal Troon on 11 over par with the projected cut set to be at six over in blustery conditions on Scotland's west coast.
A seven over par opening round left the world number two with work to do and he was never in contention to reach the weekend after dropping six shots in four holes between the third and the sixth, including a triple-bogey eight at the fourth.
"That four-hole stretch to start off is what cost me," said the Northern Irishman. "Twenty-two holes into the event and I'm thinking about where I'm going to go on vacation next week."
It is only the second time in 15 majors that McIlroy has failed to make the cut.
But his 10-year wait to add to his four majors will now stretch into 2025 at least.
The 35-year-old steadied the ship with seven consecutive pars before holing a chip from the green-side bunker at 14 for his first birdie of the day.
He picked up another shot at the 16th but still fell five short of the projected cut.
McIlroy is far from the only big name to struggle with seven of the world's top 12 set to miss the weekend.
"When the wind died down a little bit -- it was still strong enough out there -- but when it became at least manageable for me, I started to play better," he added.
"I played the last 12 in a couple under par and actually felt a little more comfortable over my shots.
"But when the wind gets that strong and you haven't played in wind like that for quite a while, sometimes it's just hard to adapt."
McIlroy's attention now turns to trying to win Olympic gold for Ireland at Le Golf National in Paris from August 1.
"I feel like I say this every Open Championship, but it's not as if we only play four events a year," he said.
"There's still a few things there's left to play for. Obviously the majors have come and gone, but (I have) to sort of refocus and try to reset for the Olympics, which will be another cool experience, and try to play well there."
McIlroy will also have a rooting interest over the weekend as his close friend and fellow Irishman Shane Lowry leads by two shots.
Lowry's only previous major win came in Northern Ireland at Portrush in 2019.
"He relishes these conditions," said McIlroy. "The Open Championship is his favourite tournament in the world. He gets more up for this than anything else.
"I'm looking forward to cheering him on and hopefully him getting his second (Claret) Jug."
