The Yazoo Brewery is located in what was once the Marathon Motor Works building. From 1910 to 1914, Marathon Motor Works made the first automobiles ever to be produced in the South. About 5,000 cars were made in those five years, earning Nashville the nickname "Detroit of the South". Despite their popularity, the hand-crafted cars were expensive and soon lost the market to the mass-produced cars of Ford and others.

Yazoo Brewery owners Lila and Linus Hall are both from Mississippi, and moved to Nashville in 1996. Linus has been brewing for over ten years, and has a craftbrewing degree from the American Brewers Guild in California, with an internship at the Brooklyn Brewery in Brooklyn, New York.