State Route 72 is a primary state highway in the southwest part of the U.S. state of Virginia. It runs from State Route 71 near Gate City north to State Route 65 at Fort Blackmore, northeast with SR 65 to Dungannon, and north via Coeburn to State Route 83 near Clintwood.

SR 72 begins at State Route 71 at Slabtown, east of Gate City. It heads north across the Moccasin Ridge via some small creek valleys and crosses Copper Creek at Williams Mill. SR 72 continues north across Copper Ridge and into the Clinch River valley, where it meets State Route 65. SR 65 and SR 72 overlap, paralleling the Clinch River to Dungannon. After the two routes split, SR 72 continues to follow the river to the northeast, but then splits in order to cross Stone Mountain.

The land flattens out near the county line, and SR 72 continues northwest and north across the Guest River and past Maytown to State Route 158 in Coeburn. SR 72 turns west with SR 158, formerly U.S. Route 58 Alternate until the bypass was built, and then splits to the north. It runs alongside small creeks, passing Bondtown and Cranes Nest on its way to Fuller Gap, where it crosses Guest Mountain and the Tennessee Valley Divide. It then descends through small creek valleys and alongside the Cranes Nest River to the county line.

SR 72 continues along the Cranes Nest River, but splits to cross a small ridge at Hibbitts Gap. Then it continues northerly alongside small creeks, past Darwin to its end at State Route 83 at Georges Fork, west of Clintwood.

The road from Coeburn north to Clintwood was part of the original state highway system designated in 1918, as a spur of State Route 11 (now U.S. Route 58 Alternate there). In the 1923 renumbering it became part of State Route 114, which continued east from Clintwood to Haysi. The piece south of Clintwood was renumbered State Route 122 in the 1928 renumbering, and that same year it was extended south from Clintwood to Dungannon and southeast to end at State Route 107 (now State Route 71). SR 122 was renumbered State Route 72 in the 1933 renumbering. In 1949, the section south of Dungannon was transferred to the secondary system as State Route 774, due to its "local character and very low traffic volume" of 187 per day. (SR 774 now carries about 360 vehicles per day.) SR 72 was extended in 1986, running southwest on State Route 65 to Fort Blackmore and then south to State Route 71 near Gate City, taking over parts of State Route 619, SR 676, SR 661, SR 710, and SR 660.