The waterway runs through the Talledega National Forest (also referred to as Choccolocco Management Area), and crosses through Calhoun, Talladega, and Cleburne counties, in central Alabama.

[4] The Choccolocco Creek Archaeological Complex near Boiling Spring, Alabama,[5][a] contains the remains of at least one temple and three burial mounds, and is an important piece of the history of early Middle Woodland period inhabitants in the area.

[6] There are indications of land usage along the creek stretching back to the Archaic Period (8,000 BC), that includes evidence of extended habitation by the Mound Builders and peoples of the Mississippian culture.

[4][5] The creek is home to over 70 species, several of which are endangered, including the pygmy sculpin (Cottus paulus), the holiday darter (Etheostoma brevirostrum), and the blue shiner (Cyprinella caerulea).

[3] The wicker ancylid (Rhodacmea filosa)—a freshwater snail once thought extinct —was surprisingly (due to episodic heavy water pollution events on the waterway) found in the creek in 2011, and is still extant as of 2023.