It has been described as being derived from the Anglicization of Native American terms, resulting in words such as Gerando, Gerundo, Genantua, Shendo and Sherando.

Throughout the war, Chief Skenandoa of the Oneida, an Iroquois nation based in New York, persuaded many of the tribe to side with the colonials against the British.

According to Oneida oral tradition, during the harsh winter of 1777–1778 at Valley Forge, where the colonials suffered, Chief Skenando provided aid to the soldiers.

Polly Cooper, an Oneida woman, stayed some time with the troops to teach them how to cook the corn properly and care for the sick.

General Washington gave her a shawl in thanks, which is displayed at Shako:wi, the museum of the Oneida Nation near Syracuse, New York.

[5][6] Despite the valley's potential for productive farmland, colonial settlement from the east was long delayed by the barrier of the Blue Ridge Mountains.

Von Graffenried reported that the Indians of Senantona (Shenandoah) had been alarmed by news of the recent Tuscarora War in North Carolina.

Governor Alexander Spotswood's legendary Knights of the Golden Horseshoe Expedition of 1716 crossed the Blue Ridge at Swift Run Gap and reached the river at Elkton, Virginia.

Known native settlements within the Valley were few but included the Shawnee occupying the region around Winchester, and Tuscarora around what is now Martinsburg, West Virginia.

The Scotch-Irish comprised the largest group of non-English immigrants from the British Isles before the Revolutionary War, and most migrated into the backcountry of the South.

[11] Governor Spotswood had arranged the Treaty of Albany with the Iroquois (Six Nations) in 1721, whereby they had agreed not to come east of the Blue Ridge in their raiding parties on tribes farther to the South.

In 1736, the Iroquois began to object, claiming that they still legally owned the land to the west of the Blue Ridge; this led to a skirmish with Valley settlers in 1743.

The Iroquois were on the verge of declaring war on the Virginia Colony as a result, when Governor Gooch paid them the sum of 100 pounds sterling for any settled land in the Valley that was claimed by them.

[13] The Shenandoah Valley was known as the breadbasket of the Confederacy during the Civil War and was seen as a backdoor for Confederate raids on Maryland, Washington, and Pennsylvania.

An associated song by James Stewart titled "The Legend of Shenandoah" was a very minor hit in 1965, reaching #133 on the Billboard Bubbling Under the Hot 100 chart.

One of the most famous cultural references to the area does not mention the valley itself: West Virginia's state song, "Take Me Home, Country Roads" by John Denver, contains the words "Blue Ridge Mountains, Shenandoah River" in the first verse.