The school announced the hire Wednesday and will hold a news conference Thursday to introduce Petrino.
Missouri State parted ways with former coach Dave Steckel on Jan. 19, with the school paying a $340,000 buyout and moving expenses. Steckel was 13-42 in five seasons with the Bears.
Petrino, 58, posted a 77-35 record at Louisville before being fired during the 2018 season. He got his first job as a head coach in 2003 at Louisville and left for the Atlanta Falcons in 2007. He posted a 3-10 record before resigning in the middle of his first NFL season.
Petrino returned to the collegiate level in 2008, coaching Arkansas until 2011. He coached at Western Kentucky in 2013 before starting his second tenure as Louisville coach in 2014.
Petrino has a 119-56 record in 14 seasons as a college football coach. He will be Missouri State's 21st coach.
The Bears posted a 1-10 record in 2019.