With a length of 52.8 miles (85.0 km), it is a major tributary of the Little Tennessee River, and is one of the primary streams draining the Unicoi Mountains.

The Tellico River and its main tributaries are renowned for their brook, brown, and rainbow trout fishing.

A 4-mile (6.4 km) stretch of the river above Tellico Plains runs parallel to the Cherohala Skyway.

In 1760 the Cherokee laid siege to the fort and defeated the garrison, in an effort to expel the British from their territory, but were later forced out themselves in the 19th century.

[4] The numerous Cherokee towns in this area were recorded by British colonist Henry Timberlake during his 1761-1762 Expedition to the Overhill region.

In the early 20th century, the Tellico River basin was logged by the Babcock Lumber Company.