Sanford is a city in the central region of the U.S. state of Florida. It is the county seat of Seminole County. As of the 2010 U.S. Census, the city had a population of 53,570. It is a principal city of the Orlando–Kissimmee–Sanford, FL Metropolitan Statistical Area, which was home to 2,134,411 people as of the 2010 U.S. Census. Known as the Historic Waterfront Gateway City, Sanford sits on the southern shore of Lake Monroe at the head of navigation on the St. Johns River.