The Bears finished 1-10 in 2019, their lone win coming against Western Illinois on Oct. 5.
Louisville fired Petrino during the 2018 season following a 2-8 start. He has a 119-56 overall record across his stops with the Cardinals, Razorbacks and Western Kentucky.
According to Yahoo Sports' Pete Thamel, Petrino agreed to a five-year contract worth $250,000 annually.
Coaching an FCS school represents a step down, but this might be the 58-year-old's best shot of working his way back to the FBS.
Petrino's Arkansas tenure ended amid controversy in April 2012.
He had gotten into a motorcycle accident. Riding as a passenger was a woman with whom he had been having an extramarital affair. The woman was also employed by the football program, with Petrino circumventing hiring requirements to bring her aboard.
After being unemployed for a year, Petrino returned to the coaching ranks with the Hilltoppers in 2013 before reuniting with Louisville in 2014.
Lamar Jackson won a Heisman Trophy in 2016, when the Cardinals won nine games and lost to LSU in the Citrus Bowl.
That was the high-water mark for Petrino during his second run at the school. Things quickly unraveled after Jackson left for the NFL following the 2017 season. Louisville had to pay Petrino a $14 million buyout to fire him, signaling how much the administration wanted to move on.
"If you want to say culture equals effort, there's something screwy going on there," athletic director Vince Tyra told reporters. "Because the effort hasn't been what it's been historically. I've told the kids that. I'm not bashful about that. They can't hide from it. It's on film."
Missouri State's calculus is obvious. Petrino has a proven track record. Only twice in his 14 years as a college head coach did his teams finish with a losing record.
However, his final year at Louisville raises questions about whether the move will work out for the Bears.