Karnes City is a city in and the county seat of Karnes County, Texas, United States. Its population was 3,111 at the 2020 census, up from 3,042 at the 2010 census. The town was named after Henry Karnes of the Texas Revolution. Karnes is 24 mi southeast of Floresville and 54 mi southeast of San Antonio on U.S. Highway 181.