Sunflower County is named for the Sunflower River, which is named in turn for the sunflowers that grow along its banks. The county was created in 1834. The land mass encampassed most of Sunflower and Leflore Counties as we know them today. The first seat of government was Clayton, located near Fort Pemberton. Later the county seat was moved to McNutt, also in the Leflore County of today. When Sunflower and Leflore Counties were separated in 1871, the new county seat for Sunflower County was moved to Johnsonville. This village was located where the north end of Mound Bayou empties into the Sunflower River. In 1882 the county seat was moved to Eureka, which was later re-named Indianola (Hemphill, Marie M. 1980. Fevers, Floods and Faith--A History of Sunflower County Mississippi, 1844-1976).

According to the U.S. Census Bureau, the county has a total area of 707 square miles, of which, 694 square miles of it is land and 13 square miles of it (1.90%) is water. Sunflower County is the longest county in Mississippi. The traveling distance from the southern boundary at Caile, to its northern boundary at Rome is approximately 56 miles.

In it's first census in 1840, there were 1,356 residents listed. In the last federal census in 2000, the population was 40,633.