Lowry sank 10 birdies in a spotless round to take a three-shot lead ahead of 2010 British Open winner Louis Oosthuizen, Richard Sterne and Mike Lorenzo-Vera and Pablo Larrazabal.
Playing in his first event since the World Cup of Golf in November, Lowry made a blistering start as he notched five birdies in seven holes from the 12th to reach the turn in 31.
The 31-year-old continued his impressive run on the back nine, rolling in three straight birdies from the first hole, and followed it up with gains on the seventh and eighth.
As well as equalling the course record set by Henrik Stenson in the inaugural tournament in 2006, the round also matched Lowry's career best from the 2009 Irish Open, which he won while still an amateur.
"I'm obviously over the moon. It equals the best score I've ever shot," Lowry said.
"I had quite a lot of time off since the World Cup but put in a decent bit of work the last two weeks over here in Dubai and I've just gone out with not much expectation but knew I was playing OK and yeah, everything clicked.
"I didn't hit as many fairways as I would have liked but I was hitting everything close and managed to hole a couple of putts, as well."
Oosthuizen, who won the South African Open last month before finishing tied-seventh at Alfred Dunhill Championship the following week, recovered from a double bogey at the 12th with birdies at the 15th, 16th and 18th.
Six more birdies on the back nine ensured Oosthuizen signed for a 65 before he was joined by compatriot Sterne and Frenchman Lorenzo-Vera in perfect scoring conditions at Abu Dhabi Golf Club.
Afternoon starter Larrazabal made it a four-way tie for the second spot after carding a stunning eagle, six birdies and a solitary bogey in his first round.
World number two Brooks Koepka, who defended his U.S. Open title and won the PGA Championship in a stellar 2018, opened with a confident 67 to share 11th spot with Belgian Thomas Pieters and Paraguayan Fabrizio Zanotti. (Reporting by Hardik Vyas in Bengaluru Editing by Christian Radnedge)