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.

Greater St. Louis is the 21st-largest metropolitan statistical area (MSA) in the United States, the largest in Missouri, and the second-largest in Illinois. Its core city—St. Louis, Missouri—sits in the geographic center of the metro area, on the west bank of the Mississippi River. The river bisects the metro area geographically between Illinois and Missouri, although the latter portion is much more populous. The MSA includes St. Louis County, which is independent of the City of St. Louis; their two populations are generally tabulated separately.