[2] Its name is in honor of Nathaniel Macon, a member of the United States Senate from North Carolina.

[3] Developed for cotton plantation agriculture in the nineteenth century, the county is considered within the Black Belt of the South.

The historic tribes encountered by European explorers were the Creek people, descendants of the Mississippian culture.

Macon County was established by European Americans on December 18, 1832, from land ceded by the Creek, following the US Congress' passage of the Indian Removal Act of 1830.

In the first half of the twentieth century, thousands of African-Americans migrated out of the county to industrial cities in the North and Midwest for job opportunities, and the chance to escape legal segregation.

Apart from the "dealignment" era between 1948 and 1972, and Herbert Hoover in the highly controversial 1928 election, no Republican has won so much as twenty percent of the county's vote in the past century.

No Republican has obtained a majority in that time span, although Dwight D. Eisenhower won a narrow plurality in 1956.

The Sheriff of Macon County is Andre Brunson, who also was the former strength coach at Tuskegee University.