Lee threw for 297 yards and ran for 105 more for the Dukes before leaving the game early. Touchdown throws went to Ishmael Hyman, Dominique Taylor and Deane Cheatham. Khalid Abdulla rushed for 102 yards and three touchdowns and Cardon Johnson added 123 yards and a score. The Dukes defense held Morehead State to just 52 rushing yards.
Lee ran for a 66-yard touchdown and threw scoring strikes to Taylor and Cheatham to help lift James Madison to a 28-7 halftime lead.
The Dukes scored 28 unanswered points in the second half, including a 66-yard touchdown throw from Lee to Hyman.
Morehead State's only score came on a 1-yard keeper by Austin Gahafer late in the second quarter.
Gahafer had 173 yards passing for the Eagles.