Barkey, who was battling for the backup quarterback job behind starter Andy Dalton, hurt his knee on his second series of the game against the Indianapolis Colts.
The NFL Network reported that Barkley suffered a grade 3 strain of the medial collateral ligament and could be a candidate to be placed on injured reserve.
The injury to Barkley likely solidified Jeff Driskel’s chances to open the regular season as Dalton’s backup.
Barkley misfired on all three pass attempts before he was injured in Thursday’s 27-26 loss to the Colts. He was signed to a two-year deal by the Bengals in March.
Last season, Barkley did not appear in a game after being on the rosters of the San Francisco 49ers and Chicago Bears.
A fourth-round draft pick of the Philadelphia Eagles in 2013, Barkley started the final six games for the Bears in 2016, finishing with a 1-5 record and throwing for 1,611 yards with eight touchdowns versus 14 interceptions.
Driskel replaced Barkley in Thursday’s game and completed 14 of 20 passes for 116 yards and a 20-yard touchdown pass to Josh Malone.
Selected by the 49ers in the sixth round of the 2016 NFL Draft, Driskel suffered a broken thumb in Cincinnati’s final preseason game a year ago and spent the season on injured reserve. He has never appeared in an NFL game.
Driskel spent parts of four seasons at Florida before winding up his college career at Louisiana Tech, throwing for 4,026 yards and 27 touchdowns in 2015.