According to the 2000 United States Census, 52.2% of the population is Native American, mostly the federally recognized Sicangu Oyate (Upper Brulé Sioux) and the Rosebud Sioux Tribe, a branch of the Lakota people.

The White River flows eastward along the north boundary line of Mellette County.

The terrain consists of semi-arid rolling hills, the northern portion dotted with ponds and small lakes.

[4] The terrain slopes to the northeast; its highest point is the SW corner at 2,779 ft (847 m) ASL.

Like most of South Dakota, Mellette County is solidly Republican.

It has not been carried by a Democrat since Lyndon Johnson’s 1964 landslide, although Barack Obama came within six votes of doing so in the 2012 election.