Depew is a village in Erie County, New York, United States. The population was 16,629 at the 2000 census. It is part of the Buffalo–Niagara Falls Metropolitan Statistical Area. The name is derived from Chauncey Mitchell Depew, the President of the New York Central Railroad and former US Senator. The Village of Depew village extends across the boundary between the towns of Lancaster and Cheektowaga. The village lies on both sides of NY Route 78 (Transit Road), a major north-south route.