[5] The Cahaba River begins in the Valley and Ridge region bounded by the Piedmont to the southeast and the Cumberland Plateau to the northwest.

The upper Cahaba forms roughly the first 100 miles, starting at the headwaters and continuing to the Fall Line, a region in which the Appalachian Mountains end and the Gulf Coastal Plain begins.

It passes through Trussville, Leeds, Irondale, Birmingham, Mountain Brook, Hoover, Vestavia, Helena, West Blocton, and Centreville.

[6][7][8] Located adjacent to the Cahaba River basin, the Moundville Archaeological Site (1000–1450 AD) was the second-largest community of the Mississippian culture.

The Bottle Creek Site (1250–1550 AD), located little more than 100 miles downriver in the Mobile-Tensaw River Delta, also influenced the region.

William Wyatt Bibb, Alabama's first governor, decided on Cahaba because of the scenery, fertile area, and navigable river ways.

However, in 1821, a steamboat, the Harriet, overcame the Alabama River's fast current and made it past Cahaba.

The river became a major trade route, which caused the city to grow, despite the removal of the capital to Tuscaloosa in 1825.

In the early 21st century, a Georgia botanist Jim Allison discovered eight unknown flower species, and later eight more were identified along the river's course that previously had not been sited in the state of Alabama.

These species feed other aquatic dwelling animals, improve water quality by eating algae, and even indicate environmental issues due to their receptiveness of pollution.

It serves as the source of drinking water in the upper course for over 1 million people and is also a popular canoeing destination.