It was named in honor of the late Revolutionary War veteran and United States Senator, Nathaniel Macon.

In Tennessee's Ordinance of Secession referendum on June 8, 1861, Macon County voted to remain in the Union by a margin of 697 to 447.

Earlier on February 9, 1861, Macon County voters had voted against holding a secession convention by a margin of 960 to 73.

[9] Macon County is located amidst the northeastern Highland Rim, and is generally rugged and hilly.

As of the 2020 United States census, there were 25,216 people, 9,170 households, and 6,215 families residing in the county.

Those Pennyroyal counties were overwhelmingly opposed to secession,[5] and a large majority of residents fought their Civil War in Union blue rather than Confederate gray.

In the 2000 election, Gore's local popularity was sufficient to give him the third-highest Democratic percentage of the past 132 years despite losing the state, but since then like all of Appalachia and surrounding regions the county has shown an extremely rapid trend to the Republican Party due to powerful opposition to the Democratic Party's liberal views on social issues.

[20] In other statewide elections, Macon County has shown a similar rapid Republican trend.

Although Phil Bredesen carried the county in both 2002 and 2006, he is the last Democratic gubernatorial candidate to top thirty percent.

North Central Telephone Cooperative is the main cable television provider in the county.