It goes east to have an interchange with SR 33 (Maryville Pike) before passing through rural areas.

SR 168 passes by the home of former Governor of Tennessee John Sevier, for which this highway is named after, before entering South Knoxville area of Knoxville to have an interchange with US 441/SR 71 (Chapman Highway).

They immediately cross a bridge over the Holston River as a 4-lane divided highway known as Asheville Highway, and continues west through neighborhoods and has an interchange with I-40 (Exit 394), where US 25W/SR 9 splits off and goes north along I-40 west.

US 11E/US 70/SR 168 continues west through neighborhoods and passing through a business district before US 11E and SR 168 both come to an end at an interchange with US 11/SR 1 (Magnolia Avenue) and the southern end of US 11W (Rutledge Pike), where US 70 continues west along US 11/SR 1.

In 1977, design proposals for a partial cloverleaf interchange at John Sevier Highway at I-40 intent to relieve truck traffic from the Forks of the River industrial park were cancelled following neighborhood opposition, citing the removal of a 24-family neighborhood near Strawberry Plains.