McIlroy birdied his closing three holes to move to 14-under par as he seeks to win the Dubai title for a second time since breaking through to claim a first professional success in the 2009 tournament.
Scotland’s Marc Warren stayed on target for a maiden Masters invitation and a fourth Tour title by shooting a 65 to sit in second place at 13 under par.
Former U.S. Open champion Graeme McDowell (65) and England’s Seve Benson (66) were a further shot back.
McIlroy started at six under par and picked up three birdies in his opening five holes.
He parred the next four before back-to-back birdies at 10 and 11 and the four-times major winner displayed his enormous class with birdies at his closing three holes.
“I’m definitely in a great position going into the weekend,” McIlroy told reporters.
"I felt like I played very nicely today and I couldn't ask for much more, bogey‑free, made birdies and set myself up for a good run over the next couple days.”
McIlroy won three events in a row last season -- the British Open, WGC–Bridgestone Invitational and PGA Championship -- but finished runner-up in his next three, the PGA Tour’s Tour Championship, DP World Tour Championship and the Abu Dhabi HSBC Championship.
“That’s not acceptable to me, especially with how I'm playing as I want to take advantage of that and I know I'm playing well enough to win,” he said.
“So there's no point in being satisfied with second, when you know you're playing well enough to lift trophies.”
Six years ago McIlroy returned home to Ireland with the gleaming ‘Coffee Pot’ trophy.
If he succeeds again this year he will arrive in Dublin on Monday staring at the likelihood of at least five days in the High Court when his dispute with a former management company will finally be resolved.
Warren, ranked 56th in the world and just six places shy of earning a first Masters invitation, was met by nearly two-year old-son Archie after his round.
“Being a father now helps me totally forget about golf, as opposed to kind of thinking about it at night time or anything like that,” he said.
(Editing by Ed Osmond)
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