The 2016 Missouri Southern Lions football team represented Missouri Southern State University in the 2016 NCAA Division II football season.

The Lions played their home games in Fred G. Hughes Stadium in Joplin, Missouri, as they have done since 1975.

[2] The Lions were led by second-year head coach, Denver Johnson.

[3] Missouri Southern has been a member of the Mid-America Intercollegiate Athletics Association since 1989.

[5] On August 2, 2016 at the MIAA Football Media Day, the Lions were chosen to finish in 10th place in the Coaches Poll, and 11th in the Media Poll.