The Hiwassee River originates from a spring on the north slope of Rocky Mountain in Towns County in the northern area of the State of Georgia. It flows northward into North Carolina before turning westward into Tennessee, flowing into the Tennessee River a few miles west of what is now State Route 58 in Meigs County, Tennessee. The river is about 147 miles (237 km) long.

The river is dammed by the Tennessee Valley Authority (TVA) in four locations, all in Western North Carolina: Chatuge Dam, Mission Dam (not owned by TVA), Hiwassee Dam, and Apalachia Dam. Water is diverted from the stream bed at Apalachia Dam and sent through a pipeline, which is tunneled through the mountains for eight miles (13 km); then it flows through the Apalachia Powerhouse to generate electricity. The stretch of the river that flows between Apalachia Dam and Apalachia Powerhouse features reduced flow. The John Muir Trail in Tennessee's Cherokee National Forest goes along this part of the river.

The 23-mile (37 km) stretch of river that flows from the North Carolina/Tennessee state line to U.S. Highway 411 near Delano is designated as a Tennessee State Scenic River (Class III Partially Developed River). For recreational purposes, it is managed by the Tennessee Resource Management Division, in cooperation with TVA. The river features Class I through Class III rapids, depending on water levels.

After exiting the mountains through a gorge, the Hiwassee broadens, meandering through rural Polk and Bradley counties in Tennessee. It is crossed by a bridge carrying US-411 soon after it exits the mountains. U.S. Route 11 passes over the river at Calhoun and Charleston, Tennessee, where local industries such as Bowater Newsprint Mill and Arch/Olin Chemical use river water in their operations.

At this point the river interfaces with the impoundment of Chickamauga Dam (located in Chattanooga, Tennessee). Many marshes and wetlands surround the main channel, providing rich habitats for wildlife and areas for hunting and fishing.

Interstate 75 passes over the river on the border of McMinn and Bradley counties. The Hiwassee continues westward; it is crossed by SR 58's bridge (this bridge replaced an old historic and narrow bridge) on its way to its confluence with the Tennessee River. This area of the river is enjoyed by boaters, fishermen, and water skiers.

Major tributaries include Valley River, Nottely River, Coker Creek, Big Lost Creek, Spring Creek, Conasauga Creek, and Toccoa/Ocoee River.

The Hiwassee River has been known by many variant spellings, particularly Hiawassee, which is also the name of the Georgia town through which the river flows. Other alternate spellings include Heia Wassea, Highwassee, Euphasee, and Quannessee. Some say the name came from the Cherokee word Ayuhwasi, meaning meadow or savanna.

The Hiwassee River passes through Murphy, North Carolina, where it flows past a site famous in Cherokee Indian mythology. The legend tells of a house-sized leech that could command the waters and use them to sweep hapless people to the bottom of the river and consume them. It was known as Tlanusi-yi, "The Leech Place."

The river flows west from North Carolina into Tennessee. This area is popular for whitewater rafting, whitewater canoeing, and whitewater kayaking. Recreational fishing is popular with several outfitters located near the river, and there is also industrial activity along the river, such as paper mills.

The Interstate 75 bridge crossed the Hiwassee between McMinn and Bradley counties in Tennessee. This was the site of a fatal 99-vehicle accident in December 1990, during extremely foggy weather in the area of a paper mill in the valley. During the years since then, a huge system of warning signs and lights has been built on that stretch of Interstate 75 to warn automobiles and trucks against incidents of foul weather, characterized by heavy rains and clouds. Many serious collisions had occurred in this area.

• Hiwassee Lake
• List of rivers of Tennessee

• Mooney, James. Myths of the Cherokee (1900, repr. 1995)
• Duncan, Barbara R. and Riggs, Brett H. Cherokee Heritage Trails Guidebook. University of North Carolina Press: Chapel Hill (2003). ISBN 0-8078-5457-3

• Hiwassee River Basin Web Site
• U.S. Geological Survey Geographic Names Information System: Hiwassee River
• Tennessee Scenic Rivers Association (TSRA)
• TVA Apalachia Release Schedule