Camilo Villegas, who owns six top-10 finishes this year, also shot a 65. He is alone in second place at 9-under-par 133. Danny Ellis, Nathan Green, Keith Huber, Charley Hoffman and Troy Matteson, a two-time winner this season, are one stroke further back at minus-8.
Chalmers got off to a rough start with a three-putt bogey on the first. He bounced right back, though, as he birdied the par-5 second. After a par on the third, Chalmers converted a birdie try on the fourth to move to minus-6.
The Australian made it two straight as be birdied No. 5. Chalmers then continued his hot play with birdies on the seventh and ninth to move to minus-9 at Hillcrest Country Club.
'That one really gave me the impetus into the back nine that I needed,' said Chalmers of his birdie on nine. 'I'm certainly used to this kind of breeze, but it was very difficult because it was gusting in different directions.'
Chalmers sank the sixth birdie of his round on the par-4 10th. The 31-year-old parred his next five holes before draining a birdie putt on the par-5 16th. He parred his final two holes.
'The game ebbs and flows and this is a chance for me to get back on the PGA Tour,' said Chalmers, who ended 156th on the PGA Tour money list last year. 'I didn't have a great year last year so I've got to do what I've got to do. I'm one of many guys at this time of year where a victory or a great week could change a lot of things.'
Villegas had a hot front nine. He birdied the second to get to minus-4. The University of Florida alum then converted a birdie chance on the par-4 fifth and made it two straight with a birdie at the sixth.
The 23-year-old made it three straight with a birdie on the par-4 seventh. Villegas parred his next four holes around the turn before dropping a shot at the par-4 12th.
Villegas moved to minus-8 with consecutive birdies from the par-4 15th. He closed with a birdie at the last to take second place.
Jason Schultz, who won the Chattanooga Classic earlier this year, shot a 4-under 67. He shares eighth place with John Mallinger (71) at 7-under-par 135.
Brent Schwarzrock, Bubba Watson, Matt Weibring, Robert Garrigus, Matt Hansen, Matt Hendrix, Brian Henninger and Eric Axley, who The Rex Hospital Open earlier this year, are one stroke further back at 6-under-par 136.
Defending champion Scott Gump struggled to a 3-over 74 on Friday, but made the cut by one stroke at 3-under-par 139. The cut line fell at 2-under-par 140 with 61 players advancing to the weekend.
Among those missing the cut was 'battlefield promotion' winner Jason Gore. Gore, who won on the PGA Tour last week and received a special exemption to play in this event, stumbled to a 2-over 73 to miss the cut at 1-over-par 143.