Walker, who is 2-3 as a starter this season, had an MRI taken over the weekend that revealed a high ankle sprain.
He finished Thursday’s game, a 25-15 victory over the Panthers' division rivals. Interim coach Steve Wilks said that Walker “sucked it up and played through it” to finish the game but will be unable to play Sunday when Carolina visits the Baltimore Ravens.
"A high ankle sprain limits his mobility... so we'll let him sit this week and go with Baker," Wilks said.
Wilks said that the Panthers will not place Walker on injured reserve, meaning it is likely he is able to return within three weeks.
Mayfield, in his first season with Carolina, won the starting job over Walker and Sam Darnold in the offseason, but was 1-4 as the starter before he suffered a sprained ankle in Week 5.
Even after Mayfield had recovered, Walker retained the starting job.
Mayfield is on pace to set career lows in completion percentage (56.6 per cent), yards per pass attempt (6.5) and passer rating (78.1).
Wilks told reporters that the top priority for Mayfield in his return is to "protect the football".
Mayfield has thrown four interceptions in his five starts and has fumbled six times this season.
As poorly as the season has started for the 3-7 Panthers, they are just two games back of the Tampa Bay Buccaneers for the NFC South lead.