The 2021 McNeese State Cowboys football team represented McNeese State University as a member of the Southland Conference during the 2021 NCAA Division I FCS football season. Led by Frank Wilson in his second and final season as head coach, the Cowboys compiled an overall record of 4–7 with a mark of 3–5 in conference play, tying for fourth place in the Southland. McNeese State played home games at Cowboy Stadium in Lake Charles, Louisiana.
Preseason
Preseason poll
The Southland Conference released their preseason poll in July 2021. The Cowboys were picked to finish fourth in the conference. In addition, six Cowboys were chosen to the Preseason All-Southland Team.