Jefferson County is located in the eastern portion of the U.S. state of Missouri. It is a part of the St. Louis Metropolitan Area. As of the 2020 census, the population was 226,739, making it the sixth-most populous county in Missouri. Its county seat is Hillsboro. The county was organized in 1818 and named in honor of former president Thomas Jefferson. In 1980, according to the U.S. census held that year, the county contained the mean center of U.S. population.