In the opening event of the 2014 tour season, Koepka fired a 7-under 64 at the CordeValle Golf Club to finish 36 holes at 131. He had eight birdies in his round along with an eagle at the par-5 15th.
Koepka, a 23-year-old American, spent this year primarily on the secondary tour in Europe. He won three times on that circuit and finished second in earnings.
Although he does not have playing status on the PGA Tour, he was granted a sponsor's exemption to play in this event and if he wins he would automatically earn playing privileges in the United States for two years. An invitation to the Masters would also come with a victory.
Koepka had a one-shot lead over Jason Kokrak, who shot a 65 for a 132 total, and a two-shot cushion over Robert Garrigus and Jim Herman.
Hideki Matsuyama, a member of the International Team that came up short against the United States last week in the Presidents Cup, was tied for 11th at 136. At No. 30, Matsuyama is the highest-ranked player taking part in this tournament.