The highway starts in rural Morrow County in Eastern Oregon at an interchange with Interstate 84 (I-84) and US 30, located east of the city of Boardman.

2,[9] travels northeast across a Union Pacific rail line and passes the Umatilla National Wildlife Refuge on the Columbia River before reaching the city of Irrigon.

US 730 continues east through the unincorporated community of McNary and the northern terminus of Oregon Route 207 (OR 207) in rural Umatilla County.

The highway turns northeastward along Lake Wallula and intersects OR 37 at Cold Springs Junction, providing connections north to the Warehouse Beach Recreation Area and Hat Rock State Park on the Columbia River and south to the city of Pendleton.

US 730 heads into Washington, traveling between a Union Pacific rail line and the canyon walls of the Columbia River Gorge.

The highway intersects its spur route and turns east towards its eastern terminus at US 12 south of the community of Wallula.

[16][23] US 730 was subsequently extended west to a new junction with US 30 and later relocated uphill due to the construction of the John Day Dam.

[29][30] AASHO approved the extension of US 12 into Washington on June 20, 1967, routing it along US 410 and SR 14 to its present terminus in Aberdeen.

[2][36] WSDOT included the road in its annual traffic survey in 2012 and calculated that 1,300 vehicles used the spur route.