Founded in 1784, Clarksville is one of the South's most historic cities. After the Civil War, traffic on the Cumberland River continued to be of great importance to the community and Clarksville became well known for its production of dark fired tobacco, its primary money crop. From 1900 to 1940, Clarksville's trade and business progressed with the growth of the town being closely connected to the county farming area.

Clarksville, the only station to become a city, was established in 1784 near the confluence of the two rivers. Education became an important theme in the county with the establishment of the Rural Academy in 1806 on the present site of Austin Peay State University.

Military activity impacted the county during World War II when the army established Camp Campbell in Montgomery County. Over 42,000 acres were purchased and in June 1942, relocation of facilities was completed. The post was named in honor of General William Bowen Campbell. On April 15, 1950, the post became Fort Campbell when it changed from a temporary installation to a permanent one.

Clarksville has the distinction of being home to the oldest bank in the state, the Northern Bank established in 1854, now AmSouth Bank; the state's oldest newspaper, The Leaf-Chronicle, established in 1808; and the first and only bank in the world established and operated entirely by women, the Women's Bank of Tennessee that opened in 1919.