Seminole County was created in 1920 from portions of Decatur and Early counties. It was named for the Seminole Indians who, faced with settlement, left their lands in the Chattahoochee River Valley and moved to the Florida Everglades. Led by their chief, Osceola, they fought two bloody frontier wars with the U.S. Army.

Donalsonville was named for Jonathan E. Donalson, a member of a prominent family who had pioneered Decatur County.