The Sycamores (8-5) trailed 16-0, but stormed ahead with 36-straight points. Perish threw a 3-yard touchdown to Robert Tonyan Jr. right before halftime. Eric Heidorn kicked a 47-yard field goal, and Perish threw scoring passes to Kyani Harris and Gary Owens to surge ahead 24-16 in the third quarter.
Mark Sewell intercepted Bennie Conney's pass on the ensuing drive and returned it 48 yards for a score. Eastern Kentucky's next three drives ended with a failed fourth-down conversion, an interception and a safety.
Dy'shawn Mobley scored on an 18-yard run and Andrew Lloyd's three field goals provided the early advantage for the Colonels (9-4).
Indiana State moves on to face eighth-seeded Chattanooga in a second round game on Dec. 6.