He played college football for the LSU Tigers and was selected by the Titans in the sixth round of the 2014 NFL draft.

On April 30, 2010, Mettenberger pleaded guilty to two misdemeanor sexual battery charges stemming from an incident at a bar near Valdosta, Georgia.

[9] With the arrival of offensive coordinator Cam Cameron in 2013, Mettenberger led LSU to a 9–3 regular season record, completing 64.9% of his passes for 3,082 yards, 22 touchdowns, and eight interceptions, with a yards-per-pass attempt of 10.41 and a quarterback rating of 171.4.

[16][17] On September 28, 2014, Mettenberger made his NFL debut in relief of Charlie Whitehurst in a 41–17 loss to the Indianapolis Colts.

[18] On October 22, the Titans decided that Mettenberger would start over both Jake Locker and Whitehurst against the Houston Texans.

[21] During a 36–7 blowout loss to the New York Giants, Mettenberger sustained a shoulder injury and missed the last 3 games.

In the 2015 season, Mettenberger played in seven games, starting four of them, to replace injured first-round rookie and starter Marcus Mariota.

Mettenberger was active for Weeks 4 and 5 (against the Kansas City Chiefs and New York Jets, respectively) as the third quarterback behind Ben Roethlisberger and Landry Jones.

He was also active as the backup for Weeks 7 and 17 (against the New England Patriots and Cleveland Browns, respectively) behind Jones, while Roethlisberger recovered from an injury against the Miami Dolphins and rested for the playoffs in the season finale.

[33] Mettenberger opened the 2019 AAF season as the third-string quarterback behind Christian Hackenberg and Brandon Silvers.

On February 25, Express head coach Mike Singletary named Mettenberger the starter.

[38] After being passed up in the 2020 XFL Draft, Mettenberger re-signed with The Spring League as starting quarterback for the Las Vegas Hughes, the host team.