The Hoosiers' Tandon Doss returned the opening kickoff 87 yards to the Hilltoppers 13-yard line, but on the second play of the drive Darius Willis fumbled and Western Kentucky (0-3) recovered.
The Hilltoppers then went 91 yards in 10 plays to score the first touchdown of the game. Bobby Rainey rushed for 62 yards during the drive, including a run of 29 yards down the Western Kentucky sideline.
Western Kentucky managed only 197 total yards the rest of the game.
Chappell completed 11 straight passes on the Hoosiers' (2-0) next two possessions. He passed for 230 yards in the first half to give Indiana a 17-7 halftime lead.
Western Kentucky had only one first down in the third quarter as the Hoosiers scored on six of seven possessions to build a comfortable 31-7 lead.
Two Hoosiers had at least eight receptions: Demarlo Belcher caught 10 passes for 135 yards and a touchdown and Terrance Turner had eight receptions for 55 yards.
Bobby Rainey carried 21 times for 110 yards and two touchdowns for Western Kentucky, but had only 48 yards after the first drive of the game. Kawaun Jakes completed 13 of 20 passes for 144 yards. Marcus Vasquez caught Jakes' lone touchdown pass with 5:24 left in the game.
Indiana converted 10 of 12 third-down opportunities, punting only once all game.