McIlroy, the tournament's defending champion played eight holes Friday, with a triple bogey, double bogey and two bogeys on his card. He'd shot even-par 70 Thursday.
McIlroy started Friday's play at the 10th hole, which he parred. But he ran a chip through the green on 11 and ended up with a 6 on the par-4 hole and poor drive left him with a bogey at 13.
After two more pars, McIlroy hit two balls in the water on No. 16, finishing with a 7 on the par-4 hole. He had a 3-putt for bogey on the par-3 17th, after which he left the course.
"I sincerely apologize to the Honda Classic and PGA Tour for my sudden withdrawal. I have been suffering with a sore wisdom tooth, which is due to come out in the near future," McIlroy said in a statement.
"It began bothering me again last night, so I relieved it with Advil. It was very painful again this morning and I was simply unable to concentrate. It was really bothering me and had begun to affect my playing partners."
He finished saying he regretted "having to make the decision to withdraw but it is one I had to make."
McIlroy is scheduled to play in next week's Cadillac Championship in Doral, Fla.