Lafayette is the most populous city in and parish seat of Lafayette Parish in the U.S. state of Louisiana, located along the Vermilion River. It is …Lafayette is the most populous city in and parish seat of Lafayette Parish in the U.S. state of Louisiana, located along the Vermilion River. It is Louisiana's fourth-most populous city with a 2020 census population of 121,374; the consolidated city-parish's population was 241,753 in 2020. The Lafayette metropolitan area was Louisiana's third largest metropolitan statistical area with a population of 478,384 at the 2020 census. The Acadiana region containing Lafayette is the largest population and economic corridor between Houston, Texas and New Orleans.