DeKalb County was created by the Alabama legislature on January 9, 1836, from land ceded to the Federal government by the Cherokee Nation. It was named for Major General Baron Johann de Kalb, a hero of the American Revolution.
DeKalb County was the one time home of the famous Cherokee Sequoyah.
The county's eastern edge, along the state line, was also the epicenter of an earthquake on April 29, 2003, measuring 4.6 on the Richter scale. Power was knocked out in the area, mirrors and pictures thrown to the floor, foundations cracked, and one chimney fell to the ground. It was felt over a significant portion of the southeastern states, including quite strongly in northeastern Alabama and neighboring northwestern Georgia, and nearby eastern Tennessee (especially near Chattanooga). It was also felt slightly in western upstate South Carolina, far west-southwestern North Carolina, south and southeastern Kentucky, and east-northeastern Mississippi.
On the whole, DeKalb County is a dry county. In 2005, a change in local laws enabled Fort Payne to become the only location in the county to allow the legal sale of alcohol. Collinsville later allowed alcohol sales.
DeKalb County saw the highest death toll in Alabama during a massive tornadic system in late April 2011 April 25–28, 2011 tornado outbreak, with 31 deaths reported in the county.