The Browns announced Mayfield will be out because of an injury to his non-throwing (left) shoulder.
Cleveland will now have to turn to Case Keenum, who is one of the top backups in the league and has made 62 starts.
Though he has never been much of a fantasy star, the 10-year veteran has shown enough to believe he can keep the offense functioning while Mayfield is unavailable. He should be able to get the ball down the field to his receivers, who could include Odell Beckham Jr.
With Jarvis Landry out with a knee injury, Beckham has become the primary target for the team in the passing attack. If he is healthy enough to play, that won't change with the quarterback switch.
Though the 28-year-old has been a risky fantasy play the past few seasons even with a healthy quarterback, his upside is obvious with his ability to turn any play into a touchdown. It's also difficult to expect Keenum to move through his progressions as well as Mayfield, which will likely result in the No. 1 option getting more targets.
It's hard to trust anyone else in the passing attack, however, in part because the combined absences of Nick Chubb and Kareem Hunt raise significant questions about the ground game. Keenum may find life difficult if the Broncos don't have to respect the run and drop more defenders back.