The area was originally claimed by Britain as part of the Clarendon settlements of the Province of Carolina, although actually populated at the time by the Cherokee.

The area was part of (though seldom actually administered by) the following jurisdictions in its early history: The county is named for General Landon Carter,[4] the son of John Carter of Virginia, who was "chairman of the court" of the first majority-rule system of American democracy, known as the Watauga Association of 1772.

The association was the first permanent settlement established outside the original thirteen American colonies and included the area that is today's Carter County.

[6] Like most East Tennessee counties, Carter Countians opposed secession on the eve of the Civil War.

[7] A railroad bridge at Carter's Depot (modern Watauga) was among those targeted by the East Tennessee bridge-burning conspiracy in November 1861.

[8] Carter County was served by the narrow gauge East Tennessee and Western North Carolina Railroad (The ET&WNC, nicknamed "Tweetsie") until the line ceased operations in 1950.

During the Local General Election on August 4, 2022, Mike Fraley overcame the Independent candidate to become Sheriff of Carter County.

[14] As of the 2020 United States census, there were 56,356 people, 23,784 households, and 15,256 families residing in the county.

Since then, only one Democrat, southerner Jimmy Carter in 1976 (who also won several traditionally Republican counties in East Tennessee), has received over 40% of the popular vote.

Most recent Carter County Mayor Rusty Barnett died on September 21, 2020.