The Staunton-Parkersburg Turnpike was an integral part of Virginia's early state road system, launched by the Internal Improvement Fund Act of 1816 and the Turnpike Act of 1817, which provided for the financing and organization of canal and turnpike companies.

The Staunton Turnpike was originally chartered by the General Assembly in 1817 with an anticipated terminus at Sistersville. This was amended in 1826, substituting Parkersburg at the mouth of the Little Kanawha River. The preliminary survey was made in 1823 by Col. Claudius Crozet, Virginia's chief engineer, who had once served in Napoleon's army and who had later taught at West Point. The road was laid through one of the most remote and sparsely populated sections of the state, conditions that delayed completion of the project.

Begun in 1831 at Staunton, seat of Augusta County, construction was almost immediately halted due to money problems. Serious work did not begin until the project was placed under direct control of the Board of Public Works in 1841. The road was not completed until 1847, when it finally reached Parkersburg. Today, U.S. 250 and State Route 47 generally follow its path.

While both the Staunton-Parkersburg Turnpike and the Northwestern Virginia Turnpike from Winchester to Parkersburg were intended by state authorities to compete with the National Road to the north, they themselves were rivals from the beginning. Unlike the Northwestern, which was placed under the authority of a state board of directors, the Staunton-Parkersburg route came under the supervision of each county it crossed. Thus it was subject to the whims and selfish interests of competing factions along the way. This was the principal reason the road was completed several years later than the Northwestern Turnpike, though the Staunton Road was also plagued with financing problems, labor and contractor difficulties, resistance to eminent domain, and intensely rugged terrain.

Portions of the road were open to wagon travel west of Staunton in 1841, and construction was completed to Beverly on the Tygart Valley River by 1843. With additional borrowing authorized by the Board of Public Works, the middle section was finished to Weston, on the West Fork River, in 1845. Delays in completing bridges over the Tygart, West Fork and Hughes rivers and their tributaries delayed full use of the turnpike. The western section from Weston to Parkersburg was completed in 1847, though travel from origin to terminus was impossible until 1850 when the last bridges were finished.

For the first time in the history of Virginia, a continuous road from Richmond to the Ohio River via Staunton was available. The historic highway is now commemorated by the Staunton-Parkersburg Turnpike National Scenic Byway, which follows much of the original route.