The 1999 Eastern Illinois Panthers represented Eastern Illinois University as a member of the Ohio Valley Conference (OVC) during the 1999 NCAA Division I-AA football season. Led by 13th-year head coach Bob Spoo, the Panthers compiled an overall record of 2–10 and a mark of 2–5 in conference play, tying for sixth place in the OVC. The team played home game O'Brien Field in Charleston, Illinois.
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