The Senedos, possibly an Iroquoian group, are thought to have occupied the area at one time, until they were said to have been slaughtered by the Catawba in the latter 17th century.

It has also been attributed to General George Washington naming it in honor of John Skenandoa, an Oneida chief from New York who helped gain support of Oneida and Tuscarora warriors to aid the rebel colonists during the American Revolutionary War.

Colonial Governor Gooch formally purchased the entire Shenandoah Valley from the Six Nations of the Iroquois by the Treaty of Lancaster in 1744.

The Iroquois had controlled the valley as a hunting ground, but European settlement had begun by that time.

During Pontiac's War (1763–1766), Shawnee efforts to repel the white intruders reached as far east as the current county.

[3] Fort Valley and the western slopes of the Massanutten Mountain are located within the county boundary.

In the 1920s it became solidly Republican at a statewide level, with the exception of Democratic local hero Harry F. Byrd and his son.

This early swing to the GOP came from the county’s rural voters being overwhelmingly German American Republicans, which overpowered the conservative Southern Democrat vote in the county population centers of New Market, Woodstock, and Strasburg.

The once strong Democratic county turned Republican due to this convention, which, according to the Shenandoah Herald, was the “…death knell of the Democratic party in the Valley counties.” The Democrats of the county were of the Jacksonian, small government stock; leading them to vote Republican after the perceived injustice by the state convention in the creation of a new constitution,[14] which was not ratified by popular vote.

The county briefly returned to its Southern Democrat roots at the state level during the civil rights movement.