Detroit won all four of its pre-season games, piling up 186 rushing yards Thursday in disposing of the Bills.
Hill hit Maurice Stovall with a 16-yard scoring pass midway through the first period and Jason Hanson added a field goal in the second, third and fourth quarters to give the Lions a 16-0 lead.
The lone Buffalo score came on a 1-yard run by Bruce Hall with 4:05 left in the game.
Hill was one of four quarterbacks used by the Lions. Starter Matthew Stafford played only one series.
Tyler Thigpen, who signed a free-agent deal with the Bills this summer, completed 12-of-21 passes for 92 yards without an interception. Buffalo had a 1-3 record in the pre-season and will open its regular campaign at Kansas City.
Detroit will start out at Tampa Bay.