DeSoto County is a county located on the northwestern border of the U.S. state of Mississippi. As of the 2020 census, the population was 185,314, making it the third-most populous county in Mississippi. Its county seat is Hernando. DeSoto County is part of the Memphis metropolitan area. It is the second-most populous county in that statistical area. The county has lowland areas that were developed in the 19th century for cotton plantations, and hill country in the eastern part of the county.