Knoxville was founded in 1823 as seat of Crawford County. It was incorporated as a town in 1825. The former city's municipal charter was dissolved in 1995 pursuant to a Georgia law that abolished city governments that were defunct or minimally operative.

Surrounding the stately historic county courthouse are monuments and historic plaques honoring notable residents, including John Pemberton, who developed the formula for Coca-Cola and was born in Crawford County near Knoxville, Georgia. Monuments to Joanna Troutman, seamstress of the forerunner to the Texas state flag, and to Georgia's first African American U.S. congressman Jefferson Franklin Long also stand nearby. Visit the Middle Georgia Pottery Museum to learn about the community's pottery tradition. Take a tour fo the Old Jail and Georgia Post and Printing Co., both on the Historic Buildings Register. Historic markers designate the Bartram Trail (William Bartram discovered Oak Leaf Hydrangea in Crawford) and the Wire Trail.