[2] The county is named for Louis Winston (1784–1824), a colonel in the militia, a prominent lawyer, and a judge of the Mississippi Supreme Court.

[3] The county is the site of Nanih Waiya, an ancient mound built in the Woodland period, about 1 CE-300 CE.

[4] As of 2008, the mound is owned by the Mississippi Band of Choctaw Indians, a federally-recognized tribe.

In 1863, during the American Civil War, the Union Army under Colonel Benjamin H. Grierson, marched through Louisville with 900 troops on a raid through Mississippi.

There are three public high schools in Winston County, Louisville High School (Louisville Wildcats), Nanih Waiya Attendance Center (Nanih Waiya Warriors) and Noxapater Attendance Center (Noxapater Tigers).

or (Winston Patriots), established in 1969 as a segregation academy,[16][17] and Grace Christian School (Eagles) in Louisville which was founded in 1970.