Under the watchful eye of tournament host Jack Nicklaus, McIlroy evoked memories of the legend with his nine-under-par 63, a round featuring two eagles and seven birdies with the double-bogey blemish.
It was good enough to push the former world No 1 three clear at the top of the leaderboard, creating the gap on Masters champion Bubba Watson, Chris Kirk and England's Paul Casey who shared second after rounds of 66.
''I felt very comfortable out there,'' McIlroy said.
''Got off to a solid start and turned in four-under without doing anything really special. And then my round sort of caught fire at the start of the back nine. I'm just really happy with my game, happy with how I played and just trying to keep this Nike Mercurial Vapor VIII TF going for the rest of the week.''
Americans Keegan Bradley, Michael Thompson and JB Holmes shared fifth at five-under.
World No.1 Adam Scott, backing up from his win in Texas, put together a decent three-under 69 to be tied 11th but couldn't keep up with playing partner McIlroy, who overcame tweaking his knee on the seventh hole.
Scott was ahead of McIlroy by a shot when he nailed a 35-foot birdie on the eighth hole to move to four-under but, just as it appeared he was cruising, the 33-year-old played a terrible approach into the ninth, dunking his ball into a creek short of the green and eventually carding a double-bogey six.
''It was just a poor shot and it stopped my momentum and then nothing really dropped on the back side,'' Scott said. ''I played overall really nice today, but killed my momentum and it's not always easy to just pick it back up and get going.''
Scott expects conditions to remain ripe for scoring and was prepared to get after McIlroy in the second round.
''I'd like to get out tomorrow and get moving in the right direction. If the conditions are good, it's going to be low scores all week,'' he said.
''I was feeling really good. My swing feels like it's gotten to a better place since last week and I feel like I'm up for it this week. Obviously, I'm going to have to chase some guys down, because there's going to be a lot of birdies.'' Ad Feedback
Fellow Australian Aaron Baddeley played the back nine first in four-over 40 but, on the front side, shot a course record-equalling 29 with seven birdies to join Scott on three-under.
Jason Day, playing for the first time since the Masters in his return from a thumb injury and also playing with McIlroy and Scott, blew off the cobwebs with an even-par 72 on his home course to be tied 45th.