Columbus is the third-largest city in Georgia, and Red Clay, White Water, and Blues is its first comprehensive history. Virginia E. Causey documents the city's founding in 1828 and brings its story to the present, examining the economic, political, social, and cultural changes over the period. It is the first history of the city that analyzes the significant contributions of all its citizens, including African Americans, women, and the working class. Causey, who has lived and worked in Columbus for more than forty years, focuses on three defining characteristics of the city's history: the role that geography has played in its evolution, specifically its location on the Chattahoochee River along the Fall Line, making it an ideal place to establish water-powered textile mills; the fact that the control of city's affairs rested in the hands of a particular business elite; and the endemic presence of violence that left a "bloody trail" throughout local history.

Causey traces the life of Columbus: its founding and early boom years; the Civil War and its aftermath; conflicts as a modern city emerged in the first half of the twentieth century; racial tension and economic decline in the mid-to-late 1900s; and rebirth and revival of the city in the twenty-first century. Peppered throughout are compelling anecdotes about the city's most colorful characters, including Sol Smith and His Dramatic Company, music phenom Blind Tom Wiggins, suffragist Augusta Howard, industrialist and philanthropist G. Gunby Jordan, peanut purveyor Tom Huston, blueswoman Ma Rainey, novelist Carson McCullers, and insurance magnate John Amos.