SR 165 begins in Tellico Plains at an intersection with SR 68 on the northwestern edge of downtown. It travels east and straddles the northern edge of downtown to have an intersection with SR 360. The highway then leaves Tellico Plains to enter the Cherokee National Forest to become narrow and curvy, running parallel to the Tellico River for several miles. SR 165 then leaves the river to climb the mountains, where it becomes extremely curvy as it gains altitude. It continues to wind its way east before coming to an end at the North Carolina state line, where the Cherohala Skyway continues as NC 143.