[4] De Kalb is named after General Johann de Kalb, a Franconian-French military officer who served as a major general in the Continental Army during the American Revolutionary War.

Mississippi Highway 39 (Main Avenue) passes through the center of De Kalb, leading north 19 miles (31 km) to Shuqualak and south 30 miles (48 km) to Meridian.

[4] As of the 2020 United States Census, there were 877 people, 480 households, and 292 families residing in the town.

37.6% of all households were made up of individuals, and 20.9% had someone living alone who was 65 years of age or older.

De Kalb is served by the Kemper County School District.