[6] The Big Sioux River rises in Roberts County, South Dakota[4] on a low plateau known as the Coteau des Prairies and flows generally southwardly through Grant, Codington, Hamlin, Brookings, Moody, and Minnehaha counties, past the communities of Watertown, Castlewood, Bruce, Flandreau, Egan, Trent, Dell Rapids, and Baltic to Sioux Falls, where it passes over a waterfall in Falls Park, which gives that city its name.

Other creek tributaries include Peg Munky Run, North Deer, Sixmile, Skunk, Split Rock, Beaver, Brule, and Pipestone.

Portions near Lake Kampeska and between Willow and Stray Horse Creeks (Codington and Hamlin counties) exceeded federally allowable levels of E. coli and fecal coliform bacteria.

[13] Features of the system include 29 miles (47 km) of levees, a floodwall in downtown, and a 15,000 feet (4,600 m) diversion channel with a dam at one end and a 118-foot (36 m) spillway at the other.

[13][14] Additionally, a greenway covers much of the river's floodplain in southern and eastern Sioux Falls, further mitigating any property damage from high water.

[16] The river overflowed its banks between September 12–15, 2019, flooding three blocks of Dell Rapids, South Dakota, and damaging up to a dozen homes.