The Titans made the switch to Tannehill while down 13-0 and following Mariota's second interception.
Mariota was 7 of 18 for 63 yards and the two picks for a passer rating of 9.5 before being pulled. He was also sacked three times.
After the game, Titans head coach Mike Vrabel was noncommital on who will be the starter moving forward, saying he'll take time to evaluate before making a decision, according to Jon Burton of NewsChannel 5.
The quarterback, who's in a contract year, has produced an up-and-down start to the season.
Mariota's had a pair of three-touchdown games (Week 1 and 4), but in the other three contests - which were all defeats - he had a combined one touchdown pass.
Tannehill, a former first-round pick, was signed in the offseason after spending the past six campaigns as the Miami Dolphins' starting signal-caller.
The 31-year-old wasn't able to lead Tennessee to any points but quickly outproduced Mariota, completing 13 of 16 passes for 144 yards and one interception.
Tannehill started 88 games in Miami, throwing for 20,434 yards and 123 touchdowns against 75 interceptions.