State Route 81 is routed along a mostly due-north path. It is a two-lane road for most of its journey, traversing rural areas of Gladyne and Slygo Counties. At Opton, State Route 81 turns northwest until State Route 806, where it turns due north again. State Route 81 continues north through Sevix, where it intersects State Route 274. State Route 81 continues north into Atrion County, then turns northwest until just south of Dwelling. It then turns due north and remains a due north path until its north end at Dragoonasag Interstate Route 92.