[2] The county was created on October 18, 1870[3] and named after the South Carolina governor and senator George McDuffie.

The Historic Wrightsborough Foundation preserves the memory of the early 12,000 acre settlement of Wrightborough, which was occupied 1768 to 1920.

[6] Most of the southern half of McDuffie County, south of Thomson, is located in the Brier Creek sub-basin of the Savannah River basin, except for a slice of the eastern portion of the county, north of Dearing and along a north–south line running through Boneville, which is located in the Middle Savannah River sub-basin of the Savannah River basin.

[7] As of the 2020 United States census, there were 21,632 people, 8,153 households, and 5,770 families residing in the county.

There were several exceptions to this, firstly between 1892 and 1908 when it supported Republican William McKinley and the Populist candidacies of James B. Weaver and favorite son Thomas E.