Mettenberger originally attended the University of Georgia but was kicked off the team due to a violation of team rules. On April 30, 2010, Mettenberger pleaded guilty to two misdemeanor sexual battery charges stemming from an incident at a bar near Valdosta, Georgia. He transferred to Butler Community College, where he became the starter for the 2010 season. In his lone season at Butler, he threw for 2,678 yards passing yards with 32 touchdowns and four interceptions. He led Butler to an 11-1 record and the JUCO National Championship game.
Prior to the 2011 season, Mettenberger transferred to Louisiana State University. In his first season at LSU, he completed eight of eleven pass attempts for 92 yards and a touchdown in limited action. In 2012, he took over as the starting quarterback. He led the team to a 10-3 record, completing 58.8% of his passes for 2,609 yards, 12 touchdowns, and 7 interceptions. With the arrival of Cam Cameron as offensive coordinator in 2013, Mettenberger led LSU to a 9-3 regular season record, completing 64.9% of his passes for 3,082 yards, 22 TD's and 8 interceptions with a yards per pass attempt of 10.41 YPA and a QB Rating of 171.4. He is the only LSU quarterback to throw for 2,500 or more yards in back-to-back seasons and was a two-time team captain. Mettenberger tore his ACL in LSU's final regular season game. He underwent surgery and just 13 weeks later, he fully participated in LSU's Pro Day. He threw nearly 125 passes while wearing a helmet and shoulder pads and completed over 90% of his passes.