The 1980 Southeast Missouri State Indians football team represented Southeast Missouri State University as a member of the Missouri Intercollegiate Athletic Association (MIAA) during the 1980 NCAA Division II football season.
Led by sixth-year head coach Jim Lohr, the Indians compiled an overall record of 4–7 with a mark of 3–3 in conference play, placing in a three way tie for third in the MIAA.
Southeast Missouri State played home game at Houck Stadium in Cape Girardeau, Missouri.
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