The county is the center of the late Eocene meteor strike that resulted in the Chesapeake Bay impact crater.

When English colonists first arrived in the area in the early 1600s, the Virginia Eastern Shore region was governed by Debedeavon (aka "The Laughing King"), who was the paramount chief of the Accomac people, which numbered around 2,000 at the time.

The northern two-thirds took the original "Accomac" name (Accomack County), while the southern third to the Point Cape Charles remained as Northampton.

[citation needed] Northampton County is notable for a colonial court case involving an indentured servant.

The first free negro (a term used prior to the abolition of slavery) in North America was Anthony Johnson of Northampton County.

[3] In 1653, Johnson brought suit in Northampton County Court to argue that one of his servants, John Casor, was indentured to him for life.

This was the first instance of a judicial determination in the Thirteen Colonies holding that a person who had committed no crime could be held in servitude for life.

Some planters sought more profitable methods of labor by taking advantage of Negro indentured servants, who had little recourse in the legal and social system to protect their rights.