O'Meara had an eagle, eight birdies and two bogeys at Oak Hills Country Club, the A.W. Tillinghast-designed course where he closed with a 63 to win the 1990 Texas Open.
'I was always counting on coming here,' O'Meara said. 'Winning in '90 was a great victory. I think it's a cool golf course.'
He made a 13-foot eagle putt on the 523-yard, par-5 15th and chipped in for birdie on the par-3 18th after pulling his tee shot by a grandstand.
'That was a big bonus,' O'Meara said.
The Texas Open moved to LaCantera Golf Club in 1995, but the Champions Tour came to Oak Hills in 2002.
John Cook, making his second Champions Tour start, and Wayne Levi were two strokes back after bogey-free 65s. Defending champion Fred Funk, Tom Kite, Tom Purtzer and 2003 champion Craig Stadler opened with 66s, and Mark James, Gil Morgan, Lonnie Nielsen, Scott Simpson and D.A. Weibring shot 67s.
There were 17 players within six shots of the lead with two rounds remaining, and 36 in the field of 78 players broke par. The sunny weather is expected to continue with temperatures in the 80s and light wind.
'With this weather and the conditions of the greens, everybody's going to make birdies,' Funk said.
O'Meara has three second-place finishes in his first season on the Champions Tour, including last week when he was eight strokes behind Bernhard Langer at the Administaff Small Business Classic in Spring.
Langer, the winner last week with a Champions Tour-record 54-hole score, had two double bogeys Friday en route to a 5-over 76.
R.W. Eaks, a two-time winner this year, bogeyed three of his first five holes before withdrawing because of a knee injury. He also withdrew last week.
Cook, an 11-time winner on the PGA TOUR, had two sub-70 rounds last week at the Administaff Small Business Classic in Spring, and finished in a tie for 36th.
'Last week, I was really anxious to play -- overanxious -- and I wasn't very comfortable for a couple of days,' he said. 'I came out this week this week and said, 'Just relax and go play.''