Mayfield aggravated an injury to his non-throwing shoulder in Sunday's game against the Arizona Cardinals on a tackle by J.J. Watt.
The move comes just a day after Mayfield declared that the decision on his playing status would be his alone. Even in the immediate aftermath of the Browns' 37-14 home loss to Arizona, the former No. 1 overall draft pick was steadfast in his determination that he would not miss a game, despite the short week of recovery for a Thursday game.
Mayfield was officially ruled out Wednesday via Cleveland's official injury report along with running back Nick Chubb (calf), while defensive end Jadeveon Clowney (ankle/chest/knee), offensive linemen Jedrick Wills (ankle) and JC Tretter (knee) and wide receiver Odell Beckham (shoulder) were listed as questionable for Thursday among a slew of banged-up Browns.
"Case Keenum will be our starter tomorrow night and we have full confidence in him to lead us and do the things necessary to put us in position to win," Browns coach Kevin Stefanski said. "Baker fought really hard to play, he's a competitor and obviously wants to be out there but just couldn't make it on a short week. We know he will continue to do everything in his power to return as quickly as possible."
Mayfield's absence will snap a streak of 51 consecutive starts. He has a chance of returning for Week 8 against the Steelers but will focus on rehab and tightening up the shoulder, NFL Network Insider Ian Rapoport reported.
Keenum completed 1 of 3 passes for 6 yards in relief of Mayfield against Arizona. His last stretch as an NFL starter came with the Washington Football Team in 2019, when he made eight starts with a passer rating of 91.3.
"Even on a short week like this, I've done it a lot so I'm excited with the guys out there," Keenum said. "I know we're uncertain on a lot of the guys, who's going to be out there, but I'm built for this. This is what I've done my whole career, not knowing if I'm going to start up until the game time, to not knowing who's out there with me, to introducing myself to players while I'm calling a play, type stuff."
Mayfield initially injured his left shoulder, a labrum tear, in a Week 2 win over the Houston Texans.