DeKalb County was created by the Alabama legislature on January 9, 1836,[3] from land ceded under duress to the Federal government by the Cherokee Nation prior to their forced removal to Indian Territory west of the Mississippi River.

The county's eastern edge, along the state line, was the epicenter of an earthquake on April 29, 2003, measuring 4.6 on the moment magnitude scale.

Power was knocked out in the area, mirrors and pictures thrown to the floor, foundations cracked, and one chimney fell to the ground.

The unusual earthquake for this region was felt over a significant portion of the southeastern states, including quite strongly in northeastern Alabama and neighboring northern Georgia, and nearby eastern Tennessee (especially near Chattanooga).

DeKalb County had one of the highest death tolls in Alabama during a massive tornadic system in April 27, 2011, the 2011 Super Outbreak.

According to the census of 2000, the largest ancestry groups in DeKalb County were English 78.31%, Scotch-Irish 8.29%, Scottish 3.33%, Irish 3.31%, Welsh 1.22%, and African 1.68%.

Eighty-four percent of its voters supported Donald Trump in 2020, and no Democrat has carried it since Southerner Jimmy Carter did so in 1976.