The veteran signal-caller suffered the concussion in last week's surprising 27-24 loss at Kansas City, but after passing a battery of tests Monday and practicing both Wednesday and Thursday, his status had been expected to be a game-time decision.
Late Saturday, the Steelers officially ruled him out, however.
"It's part of the nature of the beast of playing this game," Roethlisberger told the Pittsburgh Tribune-Review. "It's a violent sport we play."
Rookie Dennis Dixon will make his first NFL start Sunday after regular backup Charlie Batch was lost to a surgically repaired wrist injury this week. Dixon has thrown just one pass and will face one of the NFL's best pass-rushing defenses.
Roethlisberger also suffered two concussions in 2006.