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.
Reindeer recovered after escaping from Santa during lighting ceremony
Wisconsin business offering 'therapeutic cuddling' forced to close