The Eagles (2-4), rebounding from a heartbreaking loss to Fredericktown last week, broke out strong with 21 first-quarter points.
"We could have had a big letdown after last week," said East Prairie coach Jason Aycock, "but the kids responded well. They keep bouncing back."
Chaffee (0-6) had no answers for the Eagle offense, led by running back Dez Johnson who rushed for 201 yards on 18 carries.
Johnson scored on runs of 2, 35 and 55 yards and caught touchdown passes of 57 and 61 yards. He also threw for a two-point conversion and ran another.
Preston Shoemaker, the East Prairie signal caller, had a productive evening with five touchdown tosses, while also rushing for 46 yards on five carries.
Besides the two scoring strikes to Johnson, Shoemaker hit Anthony Smith on touchdowns of 29 and 39 yards and Randy Woods on a 6-yarder.