The route originally continued westward from downtown Cleveland, crossing the Tennessee River at a ferry in Hamilton County, through Soddy-Daisy and across the Cumberland Plateau, and joined where the concurrency splits from US 41 (now part of Interstate 24) near Pelham.

[2] TDOT plans to remove the designation of US 64 from the Ocoee Scenic Byway, and build a new four lane route, due to the high volumes of commercial traffic passing through the area.

[3] In 1986, TDOT began preparations to widen the entire segment of US 64 between Memphis and Pelham to four lanes, a distance of about 266 miles (428 km), or about 70% of the length of the route in Tennessee.

[citation needed] In November 2009, a massive rock slide closed the Ocoee Scenic Byway for several months.

The route unofficially runs concurrent with I-24 across Monteagle Mountain, the stretch across the Cumberland Plateau, often cited as one of the most hazardous stretches of highway in the United States and splits at exit 152 near Kimball where it then enters Jasper, becoming concurrent with US 41, of which it crosses Nickajack Lake, part of the Tennessee River to Chattanooga.

The section beginning in Cleveland and continuing into North Carolina is part of Corridor K of the Appalachian Development Highway System.

State Route 433 (SR 433) is the unsigned designation for US 64’s southern and eastern bypass of the cities of Winchester and Decherd in Franklin County, Tennessee.