The Spaniard's overall score of 12-under 132 matches the 36-hole low at the 7,441-yard Golf Club of Houston, and he's one shot ahead of Matt Kuchar.
Garcia, opening on the back nine, climbed the leaderboard with a birdie-eagle-birdie stretch on his front nine. His eagle on No. 13 came after sticking his 282-yard second shot to within five feet.
“I mean, obviously I feel good, but every week is different,” Garcia said. “First of all, we got to finish this week, and hopefully next week I'll be feeling good (and) not too many things will be bothering me health-wise, and then just feel good on the course, hopefully play well and things happen.”
Phil Mickelson shot a two-under 70 and is 6 under overall, six shots back of Garcia.
After a bogey-free opening round on Thursday, Mickelson -- still recovering from last week's muscle pull that forced his withdrawal from the Texas Open -- overcame a pair of bogeys on Friday with four birdies.
The five-time major winner, who won the Houston Open in 2011, had back-to-back birdies to reach six under and is one of 11 golfers within six shots of Garcia.
Kuchar, who tied for fourth last week in San Antonio, began his afternoon round six shots back of Garcia after opening with a six-under 66 on Thursday.
He reached 12 under with his sixth birdie of the day on the par-four 17th before finding the fairway bunker on the 18th and settling for a bogey to fall back to 11 under.
“If we get some rain and it doesn't blow too hard, of course the course will soften up and the scores will go even lower,” Kuchar said. “No telling … It could be really tough.”
While the clear and windy conditions presented difficulties for several in the field, Garcia had no such problems in just his second visit to the former Redstone Golf Club — which switched names to the Golf Club of Houston after an ownership change.
Still in search of his first major championship, Garcia showed he's ready for the slick greens and tight fairways at next week's Masters on the Augusta National-like setup on Friday. He needed only 25 putts for his round while finishing only two shots off the course record of 63.
He equaled the course's previous low 36 holes set by Johnson Wagner in 2008 and matched in 2012 by Jeff Maggert.
Garcia, who opened with a five-under 67 on Thursday, began Friday's round on the back nine. His first birdie came following a 12-foot putt on No. 12, and he followed that with a spectacular eagle on the par-5 13th.
He started the 592-yard hole with a 307-yard tee shot, following that with a 282-yard three-wood to within five feet of the hole. The eagle putt sent him into the lead at eight under, and he then birdied the par-three 14th before putting together three straight birdies on his back nine.
The 34-year-old Garcia finished in a tie for 77th in his only other visit to the Houston Open in 2009, including a final-round 81.
Garcia and Kuchar will be paired in Saturday's final group along with one of the four players who are at eight under. Tournament officials said they will assign threesomes and send the pros off both tees early in the morning to try and beat expected rain on Saturday afternoon.
Matt Jones, Cameron Tringale, Jimmy Walker and Shawn Stefani are tied for third at 8 under, while Steve Stricker and Ben Curtis are at seven under. Walker, who leads the PGA Tour with three wins this season, matched Garcia's seven-under 65 on Friday.
Defending champion D.A. Points missed the cut after shooting a two-over 74 on Friday and finishing 1 over overall.