George will replace former Tigers coach Ron Reed, who had been with Tennessee State since 2010. Reed compiled a 60-69 record at the school.
George, a member of the College Football Hall of Fame, starred at running back for the Titans from 1996 to 2003. Before his time in Nashville, he played at Ohio State and won the 1995 Heisman Memorial Trophy.
The four-time Pro Bowl selection's No. 27 is retired by both the Buckeyes and the Titans.
The Tigers are hoping George will provide a spark to the program. The school is taking a similar approach as Jackson State, which hired former NFL star and Pro Football Hall of Famer Deion Sanders in September to lead its football program.
Sanders has guided Jackson State to a 4-3 record in his first season as head coach. Like Sanders, George doesn't have extensive coaching experience.
George has served as a mentor for multiple Titans players, including current tailback Derrick Henry.