Ferby scored on touchdown runs of five and two yards in his return after missing 2016 with a shoulder injury.
The two-time defending Conference USA champion Hilltoppers led 17-0 at halftime and held off a two-score rally in the third quarter from FCS-member Eastern Kentucky.
Tim Boyle threw two TD passes to Ryan Markush in the third to bring the Colonels within 24-14, but Western Kentucky pulled away to win its sixth-straight season opener.
Boyle completed 29 of 45 passes for 320 yards, 107 of which went to Markush on seven receptions.
Mike White completed 20 of 31 passes for 264 yards and a 66-yard touchdown strike to Lucky Jackson in the second quarter for Western Kentucky. Jackson had 144 receiving yards on five grabs.
Western Kentucky won the 86th meeting against Eastern Kentucky, the most-played game between two Kentucky schools. The rivalry returned after an eight-year hiatus, the longest break since the series began in 1914.