[3] The county is named after General "Mad Anthony" Wayne, a prominent military leader in the American Revolutionary War.

[1] Like several other counties on the Western Highland Rim near the Tennessee River, Wayne County was largely pro-Union during the Civil War, contrary to the generally pro-Confederate sympathies of West and Middle Tennessee.

In Tennessee's Ordinance of Secession referendum on June 8, 1861, Wayne County voted to remain in the Union by a margin of 905 to 409.

Earlier on February 9, 1861, Wayne County voters had voted against holding a secession convention by a margin of 737 to 255.

As of the 2020 United States census, there were 16,232 people, 5,764 households, and 4,016 families residing in the county.

No Democratic presidential candidate has carried the county since Samuel J. Tilden in the controversial 1876 election.

[16] On rare occasions, the county has voted for Democratic candidates for U.S. Senate and state governor.

Al Gore carried Wayne County in his 1990 reelection bid, though he never carried in either 1992 or 1996 as Bill Clinton's vice presidential running mate or his campaign for the presidency in 2000, in which he also lost his home state.