Mississippi Highway 16 is a state highway in central Mississippi. It runs east–west for 186.4 miles (300.0 km), from the Mississippi Delta region to the Alabama state line. MS 16 serves 8 counties: Issaquena, Sharkey, Yazoo, Humphreys, Madison, Leake, Neshoba, and Kemper.

Yazoo County is a county located in the U.S. state of Mississippi. As of the 2020 census, the population was 26,743. The county seat is Yazoo City. It is named for the Yazoo River, which forms its western border. Its name is said to come from a Choctaw language word meaning "River of Death".