By the time of the Civil War, riverfront landings had been developed by the many large cotton plantations worked by slaves, who outnumbered the white residents of the county.

[3] The American Civil War devastated the local economy, completely destroying the plantation-based infrastructure of Chickasaw County.

The newly freed slaves had to adapt to the new labor system, in which the white landowners still retained partial control over their lives through the practice of sharecropping.

The economy declined again in the late 19th century, when falling cotton prices reduced both black and white residents to poverty.

According to the census[12] of 2000, the largest ancestry groups in Chickasaw County were English 44.1%, African 41% and Scots-Irish 13.5%.

Candieland, the plantation of the fictional Calvin Candie, played by Leonardo DiCaprio in Quentin Tarantino's film Django Unchained, is located in Chickasaw County.

[16] Titus Andromedon, from the Netflix series Unbreakable Kimmy Schmidt, is from Chickasaw County