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The area originally was inhabited by the Umpqua Indians, a grouping of natives who spoke a variety of Penutian and Athabaskan languages. Following the Rogue River Indian War in 1856, most of the remaining natives were moved by the government to the Grand Ronde Indian Reservation. However, seven families of Umpqua hid in the hills, eluding capture for many decades. They are now federally recognized as the Cow Creek Band of Umpqua Tribe of Indians. The tribe manages a small reservation in Canyonville, Oregon, and has a Casino/Hotel named Seven Feathers to represent the seven families who refused forced removal to the Grand Ronde Reservation.
Douglas County was created on January 7, 1852, from the portion of Umpqua County which lay east of the Coast Range summit. In 1856 the Camas Valley was annexed to Douglas County from Coos County. The county is named for Illinois Senator Stephen A. Douglas. In 1862, the rest of Umpqua county was absorbed into Douglas County, some say due to the loss of population following the end of the early gold boom, while others attribute the absorption to politics. Further boundary adjustments were made with Jackson and Lane Counties in 1915. The borders of Douglas County are largely defined by the Umpqua River watershed.
In 2017, after the defeat of a referendum, the Douglas County Library System ceased operations and all public libraries in the county were closed. Subsequently, 10 of the cities reopened their libraries to continue serving their communities.