John Huston, the course-record holder at Muirfield Village with a 61 in 1996, carded a 6-under 66 on Thursday to sit alone in third place.
Tiger Woods returned to action on the PGA Tour for the first time since the Masters and posted a 5-under 67. He is tied for fourth place with Byron Nelson winner Vijay Singh, 2001 U.S. Open champion Retief Goosen, Chad Campbell, Brad Faxon, Adam Scott and two-time U.S. Open winner Lee Janzen.
Woods drained a five-foot birdie putt at the second but traded a bogey for a birdie at No. 6 and 7. Woods caught fire around the turn with a pair of short birdie putts at 10 and 11 but the top-ranked player in the world dropped a shot at No. 12.
Woods ran home a seven-foot birdie putt at 13 and closed with birdies at 15 and a 25-footer at 18 to polish off his round of 67.
'The scores are so low today,' said Woods, who won this tournament three years in a row from 1999-2001. 'It's hard to believe that 4-under is probably not going to be in the top-10. You don't see that on this golf course.'
Winds were down so scores were lower than years past and bad weather never reached the course. Thursday's first round was only the fourth in 14 years that had no weather delays.
Howell parred the first three holes Thursday but played a brilliant 6-iron to inches to set up birdie at No. 4. He parred the fifth but dropped a shot at the sixth when his second pitched short of the green and fell back into water. Howell did well enough to make bogey from 100 yards but a two-putt birdie at seven and a 10-footer for birdie at eight got the 23-year-old back on track.
Howell continued his strong play on the second nine when his 9-iron at the 10th landed eight feet from the hole and he converted the birdie putt. At the 13th, Howell hit driver-sand-wedge to 10 feet for birdie No. 5 of his round.
His length came in handy at the par-5 15th. Howell hit 3-wood off the tee then knocked a 4-iron to 15 feet where he rolled home the eagle putt to reach 6-under par for the round.
Howell closed out his round in impressive fashion. He played a 6-iron to 15 feet at the 17th to set up birdie then holed a 45-footer for birdie at the last to own a one-shot lead.
'The conditions today were perfect for good scoring. There was no wind,' said Howell, who earned his only PGA Tour victory at last year's Michelob Championship at Kingsmill. 'I like to hit driver, I like the big fairways, I just like the whole place. The golf course seems to fit me well.'
While Howell teed off in one of the earlier groups Thursday, Perry played later in the afternoon when the wind picked up.
Perry, who bested Hale Irwin in a playoff to win the 1991 Memorial, was 1-under par through seven holes thanks to a pair of birdies and a bogey. At the eighth, Perry hit a 7-iron pin-high and sank the 10-foot birdie putt.
Perry laid up short of the green at the par-5 11th and wedged his third to six feet. He ran home the birdie putt and added a 30-foot birdie two holes later to get to 4-under par for the tournament.
The Colonial champion ended his round in style. He birdied the par-5 15th then holed a four-foot birdie at 17 and a seven-footer at 18 to gain sole possession of second place.
'I only had four previous wins until last week. I never really did that well the next week out,' said Perry. 'I was trying to push a little harder to see if I could step up to the next level and push my game a little harder. I'm in a little hot streak.'
Defending champion Jim Furyk is part of a group tied for 11th including Jeff Maggert and John Daly.