D'Andre Ferby added two touchdown runs for the Hilltoppers (4-1, 2-0 Conference USA), who piled up 504 yards.
Doughty finished 28 of 38 and moved into the top 100 in NCAA for career passing yards with 9,800. He connected with Taywan Taylor for 10 yards, Jared Dangerfield for 39 and Antwane Grant for 45 in the first quarter. In the second he connected with Tyler Higbee for 30 yards to make it 28-3.
Doughty has thrown for 400-plus yards in six of his last seven games with an average of 356 yards in the first half of the last three after having 343 against Rice.
Western Kentucky turned five Rice (2-3, 0-1) turnovers into touchdowns.
Darmontre Warr also ran for a Western Kentucky touchdown.