The Missouri Valley Football Conference's first season was in 1985 (then known as the Gateway Conference), and Missouri State defeated Southern Illinois, 40-28, on Sept. 7, 1985, in the first-ever league game. Since the league's inception, a total of 11 different members have played in the conference. 

Eastern Illinois (now in the Ohio Valley Conference) is the only charter memter to leave the Gateway. The league has been stable with only five changes since 1986: Eastern Illinois withdrew in 1995; Youngstown State was admitted in 1997; Western Kentucky (now in the Sun Belt Conference at the Football Bowl Subdivision level) was admitted in 2001 and withdrew after the 2006 season; and North Dakota State and South Dakota State were admitted for the 2008 season.