Chamberlain is a city in Brule County, South Dakota, United States. It is located on the east bank of the Missouri River, at the dammed section of the Lake Francis Case, close to where it is crossed by Interstate 90.

Lake Francis Case is a large reservoir impounded by Fort Randall Dam on the Missouri River in south-central South Dakota, United States. The lake has an area of 102,000 acres (410 km2) and a maximum depth of 140 ft (43 m). Lake Francis Case has a length of approximately 107 mi (172 km) and has a shoreline of 540 mi (870 km). The lake is the eleventh-largest reservoir in the United States and is located within the counties of: Charles Mix, Gregory, Lyman, Brule, and Buffalo. The lake stretches from Pickstown, South Dakota upstream to Big Bend Dam.