Leftwich played quarterback for 10 seasons in the NFL, spending time with the Jacksonville Jaguars (2003-06), Atlanta Falcons (2007), Pittsburgh Steelers (2008, 2010-12) and Buccaneers (2009). He started 50-of-60 career games, completing 930-of-1,605 passes (57.9 pct.) for 10,532 yards, with 58 touchdowns and 42 interceptions. He earned a Super Bowl ring with the Steelers following the team's victory in Super Bowl XLIII.

Leftwich played quarterback for 10 seasons in the NFL, spending time with the Jacksonville Jaguars (2003-06), Atlanta Falcons (2007), Pittsburgh Steelers (2008, 2010-12) and Buccaneers (2009). He started 50-of-60 career games, completing 930-of-1,605 passes (57.9 pct.) for 10,532 yards, with 58 touchdowns and 42 interceptions. He earned a Super Bowl ring with the Steelers following the team's victory in Super Bowl XLIII.

In 2016, Leftwich began his coaching career, working as an intern coach with the Arizona Cardinals, before being hired as the team's quarterbacks coach in 2017. The 2017 season saw Arizona become the first team to have three different quarterbacks (Carson Palmer, Blaine Gabbert, Drew Stanton) win multiple starts since 2007. In 2018, Leftwich added the responsibility of offensive coordinator to his duties during the season.

A first-round pick (seventh overall) of the Jaguars in 2003, Leftwich spent four seasons with Jacksonville, including helping the team earn an AFC Wild Card berth in 2005. Leftwich, who played collegiately at Marshall, set Mid-American Conference records for passing yards and total offense during his collegiate career, while twice being named MAC Offensive Player of the Year (2001-02). He finished sixth in voting for the Heisman as a senior in 2002 and was inducted into the Marshall Hall of Fame in 2007.