The title holder frittered away stroke after stroke at the European Tour's flagship event and his five-over total of 149 meant he missed the cut by a considerable margin.
McIlroy is in the middle of an untypically busy schedule of five tournaments in a row that will end with the Irish Open event he hosts at Royal County Down next week.
The 26-year-old Northern Irishman cruised to a seven-shot win at the Wells Fargo Championship in North Carolina last weekend but he says his trans-Atlantic exertions had finally caught up with him.
"I'm a little disapppointed I'm not going to be here for the weekend," said McIlroy, who also won the WGC-Cadillac Match Play in California at the start of the month.
"I'd still rather be here but it's not all bad getting to go home for the weekend. If there was any weekend to miss, coming off the back of three good weeks in the United States, I'm probably in need of a little bit of a rest."
McIlroy seemed out of sorts from the start as he found five bunkers in six holes.
On the second the four-times major winner mouthed "did you see that?" at a television camera, as if to complain about the uneven greens, when his putt hit a bump and stopped well short of the hole.
He perked up by bagging a birdie at the short eighth, arrowing a pinpoint five-wood within a few feet of the cup.
McIlroy then dropped another stroke at the 10th before snap-hooking his drive left at the 11th and slumping to a double-bogey six.
More bogeys followed at the 13th and 16th. He almost chipped in for an eagle at the 17th but the three putts he took from 20 feet at the last capped a miserable day.
After missing the cut for only the third time in 45 tournaments, McIlroy said: "Any time you are defending a title you want to come back and give it a valiant effort."
"It was inevitable at some point the run was going to come to an end. Now I just dust myself off and get ready for next week at the Irish Open."