There are 7 US Post Offices in Desoto County serving a total of 147,746 residents equating to 21,107 residents per post office. It's estimated that approximately 235,819 packages are handled across the 7 county post offices annually. DeSoto County is a county located in the U.S. state of Mississippi. As of the 2010 census, the population was 161,252, making it the third-most populous county in Mississippi. Its county seat is Hernando. DeSoto County is part of the Memphis, TN-MS-AR Metropolitan Statistical Area (MSA). It is the second-most populous county in the MSA. The county is part of the Mississippi Delta and hill country.