The Huskies (6-3, 4-1 Mid-American) won their third straight games, scoring on five straight possessions to take a 37-6 halftime lead.
Spann had scoring runs of 65 and 79 yards in the first half, and DeMarcus Grady threw 30- and 31-yard touchdown passes to Landon Cox. Grady passed for 119 yards, ran for 104 and had a 5-yard scoring run in the third quarter.
Eastern Michigan (0-9, 0-5) twice drove inside the Northern Illinois 5 in the first quarter, but reached Huskies territory just once the rest of the way.
Dwayne Priest ran for 75 yards for the Eagles.