Roethlisberger was injured early in the second half of the Steelers' game Monday against Kansas City. He has since been diagnosed with a sprained sternoclavicular joint in his right shoulder.
Leftwich finished Monday's game at quarterback for Pittsburgh, which won 16-13 in overtime.
Leftwich, in his 10th season in the NFL, is 24-25 as a starter. Sunday's home game against the Baltimore Ravens will mark Leftwich's first starting assignment since Sept. 27, 2009, when he was playing for the Tampa Bay Buccaneers.
Pittsburgh (6-3) is one game behind Baltimore in the AFC North standings.
Leftwich completed 7-of-14 passes Monday for 73 yards. In his career, he's completed 58.2 percent of his passes for 10,333 yards with 58 touchdowns and 41 interceptions.