Sean Murphy matched Rodriguez' 7-under 65 to move into a share of second place. He stands at 6-under-par 136 and is tied for second with overnight leader David Branshaw, Zoran Zorkic and Steve Ford.
Rodriguez started his round on the front nine of the East Course at the Country Club of Hershey. He notched his first birdie of the day at the par-4 fourth. He moved to minus-3 for the tournament with a birdie at the par-5 fifth.
The 30-year-old caught fire around the turn. He birdied No. 10 and made it two straight with a birdie at the next. Rodriguez jumped to 6-under when his pitching-wedge to the par-4 12th found the bottom of the cup for an eagle.
Rodriguez stumbled to a bogey at the par-3 16th. He recovered to take first place by himself with a birdie at the last.
'I saw my name near the top of the board yesterday and I got a little nervous,' said Rodriguez. 'I hadn't been up there in a while. Today, it wasn't about a score. It was about moving up. I guess we'll have to reevaluate now for tomorrow.'
Rodriguez nearly quit the game after struggling at the Virginia Beach Open earlier this season. But has since worked with a sports psychologist to get his mind back on his game.
'After Virginia Beach, I said I was done,' Rodriguez said. 'I've come close to quitting golf a couple times but this time I was done. We figured out that the harder I press, the worse I do. Now, I just try to take one shot at a time.'
Murphy got going midway through the front side, his opening nine. He rolled in back-to-back birdies from the sixth and did the same from the ninth to make it four birdies in a five-hole stretch.
After a pair of pars, Murphy rolled in a birdie putt at the 13th. He converted another birdie try on 14 to make it two straight.
Murphy, a six-time winner on the Nationwide Tour, got to 7-under for his round with a birdie at the 16th. However he stumbled to a bogey on the next hole to fall into a share of second place.
Branshaw, who owned a three-shot lead entering the round, had success on the front side but struggled on the inward half. He birdied the fourth and sixth to head to the back nine at minus-9. But trouble loomed around the turn.
He dropped a shot at the 11th, but recovered with a birdie at the next. Branshaw however struggled to a double-bogey at the 15th and dropped another shot at No. 17 to finish a round of 1-over 72.
Zorkic had three birdies in his first five holes to start quickly. He made the turn to the front nine, where he birdied Nos. 1 and 7 to get to 7-under. He slipped back one shot with a bogey at the par-3 eighth.
Ford had a similar start to Zorkic. He birdied three of his first five holes on the front side. He struggled to bogeys at the 11th and 13th, but snuck in a birdie at No. 12. He erased the other bogey with his final birdie of the day at the 17th.
Paul Claxton, Zach Johnson, Mark Wurtz and Roger Tambellini share sixth place at 5-under-par 137.
The cut line fell at 1-over-par 143 with Rob McKelvey and long-hitting Victor Schwamkrug surviving on the number.