On September 21, 2020, Deion Sanders became the 21st head coach of the Jackson State Tigers, a team in the second level of NCAA football, the Division I Football Championship Subdivision (FCS), that represents the historically black (HBCU) Jackson State University.

In his first season in spring 2021, abbreviated and delayed from its normally intended fall 2020 schedule due to COVID-19 disruptions, he led the Tigers to a 4–3 record, with one win by forfeit. In the fall 2021 season, Sanders led the Tigers to the Southwestern Athletic Conference (SWAC) title and a program record of 11 wins, also being named the recipient of the fall 2021 Eddie Robinson Award as the season’s top FCS head coach.

Sanders notably flipped the recruitment of defensive back Travis Hunter who was the number one overall recruit in the 2022 class. Hunter initially committed to Sanders’ alma mater Florida State. The move was heralded by recruiting director Steve Wiltfong; he said it was “the biggest signing day moment in the history of college football” as Football Championship Subdivision programs and the HBCUs that compete at such a level of competition are not usual destinations for high level recruits out of high school.[45] Hunter was the first five star recruit to sign with an FCS program.

Sanders led Jackson State to a 27−6 record during his three seasons at the helm.