The Northern Irishman, who recorded top-three finishes in three of the last five majors, fired a flawless seven-under-par 65 to set the early pace before being caught late in the day by Spaniard Alvaro Quiros, who birdied the last two holes.
South Korean Yang Yong-eun, who became Asia's first major winner at the 2009 PGA Championship, bogeyed the last two holes for a 67 to end a fascinating day of low-scoring level with compatriot KJ Choi.
Americans Matt Kuchar and Ricky Barnes opened with 68s while four-times winner Tiger Woods, bidding for his first tournament win in almost 17 months, narrowly missed birdie putts on 15 and 16 before signing for a 71.
Defending champion Phil Mickelson, seeking his fourth Masters title, was three-under playing the last before missing the green with his approach to record his only bogey of the day for a 70.
In near-perfect spring weather at Augusta National, McIlroy birdied three of the first four holes and negotiated the tricky Amen Corner loop, from 11 to 13, in one-under before picking up further shots at the 14th and 15th.
"I drove the ball really good and when you drive it well, you have a chance to give yourself opportunities for birdies," the 21-year-old told reporters.
At last year's British Open, McIlroy collapsed from a record 63 to a second-round 80 in brutal winds at St Andrews but he felt he could only learn from that experience.
Woods, who has finished no worse than tied for sixth in his last six Masters appearances, made a confident start to reach the turn in one-under 35.
He sank a 14-footer to birdie the par-three sixth but then faltered at the 10th, where he missed a par putt from six feet, and also at the 11th, where he drove into pine trees. Although he rebounded with birdies at 13 and 14, he failed to capitalise on further opportunities over the closing holes to end the day six strokes behind the pacesetting McIlroy.
Atwal starts poorly
It was not a happy debut at the US Masters for Arjun Atwal, only the second Indian to play at the fabled course, as he ended at tied 97th with a eight-over 80 after the opening round.
Atwal had a disappointing second nine during which he had three double bogeys. Overall, Atwal had just one birdie, one eagle, two bogeys and four double bogeys in a highly eventful and roller-coaster round.
Leading scores (after 18 holes): 65: Rory McIlroy (GBR), Alvaro Quiros (Esp); 67: Yang Yong-eun (Kor), KJ Choi (Korea); 68: Matt Kuchar (US), Ricky Barnes (US); 69: Ross Fisher (GBR), Brandt Snedeker (US), Sergio Garcia (Esp), Charl Schwartzel (SA), Trevor Immelman (SA), Geoff Ogilvy (Aus), Gary Woodland (US).
