Williams suffered a quad contusion last week at Miami when a player's helmet caught him in the thigh area.
The eight-year veteran leads Carolina in rushing with 610 yards, but he hasn't run for more than 46 yards in a game the past six weeks.
Carolina will go with Mike Tolbert, Jonathan Stewart and rookie Kenjon Barner. Coach Ron Rivera called them a "formidable" group on Friday and doesn't expect there to be a drop-off in the running game.
Defensive end Charles Johnson (sprained knee) will miss his second straight game.