Mariota departed with less than one minute left in the first half after he was sacked by defensive end Jonathan Allen. He appeared to land hard on his right throwing elbow, although the NFL Network's Melissa Stark said the stinger was in the shoulder area.
Blaine Gabbert, who was 36-for-61 passing with two touchdowns and two interceptions while appearing in six games this season (two starts), replaced Mariota.
Mariota sustained a nerve injury in his right elbow in Tennessee's Week 1 loss at Miami, forcing Gabbert to start the next two weeks.
Mariota entered Saturday's game with 11 touchdowns and eight interceptions while completing 68.6 percent of his passes. He also rushed for 350 yards and two scores.
Mariota, the No. 2 overall selection in the 2015 draft by the Titans, was already limited in practice this week with a foot injury.