Mayfield entered Sunday’s game with a rib injury and was questionable to play.
The former No. 1 pick completed 10 of 18 passes for 119 yards and one touchdown against two interceptions before being pulled.
Mayfield had taken four sacks, with the Steelers’ front seven dominating the Browns’ offensive line.
“Oh, yeah. Mama didn’t raise no wuss,” the quarterback said Monday when asked about potentially playing through the injury.
Keenum previously worked with Browns head coach Kevin Stefanski while the two were with the Minnesota Vikings. He joined Cleveland this offseason.
Mayfield led the Browns to a 4-1 record to start the campaign, throwing nine touchdowns versus just four interceptions. But Cleveland is now facing an uphill battle to catch the undefeated Steelers in the race for the AFC North barring a miraculous fourth-quarter comeback.