Koepka, in action for the first time in the 2019-20 season, followed up his opening-round 70 with an even-par 71 during the second round in Las Vegas on Friday.
The world No. 1 was unable to get going, his difficult round including a double bogey at the par-four 11th hole.
Koepka — runner-up at the 2017 tournament — ended up at 1 under, well back of the cut line of 5 under in Nevada.
Kevin Na produced the round of the day as the American fired a 9-under 62 to be part of a four-man leading pack.
Na charged into 12 under to sit alongside Brian Stuard (65), Patrick Cantlay (64) and Lucas Glover (63) atop the leaderboard.
The 2011 champion, Na produced a brilliant finish to his round, making eagles at the par-five 13th and 16th before birdies on the final two holes.
Cantlay has enjoyed the tournament in recent years, finishing runner-up last year after winning the event in November 2017, and is in contention once more.
Australian Matt Jones fired an 8-under 63 to be outright fifth at 11 under.
Defending champion Bryson DeChambeau (68) sits back in a tie for 21st at 8 under in a group that includes Phil Mickelson (69).
