European settlement remained sparse over the subsequent decades, though the English established a small for on the northern shore of Lake Mattamuskeet.

In 1711, Algonquin-speaking Native Americans in the area joined with the proximate Tuscarora people in launching a war against the settlers.

The conflict was won by the settlers in 1715, with many captured Native Americans enslaved and the remaining Tuscaroras largely expelled from North Carolina.

The local Algonquin natives were gathered on the newly created Mattamuskeet Reservation, which comprised most of the eastern mainland section of what eventually became Hyde County.

The name Wickham was derived from the manor of Temple Wycombe in Buckinghamshire, England, the family home of John Archdale, governor of North and South Carolina from 1695 to 1696.

[4][10] In 1834, an "apprenticeship" program was begun whereby local Native American children were placed under the tutelage of white families to learn trades.

[12] Ocracoke benefitted from a modest shipping industry which persisted into the mid-1800s, while the mainland portion of county was largely agrarian, though farmers struggled in the swampy terrain.

[13] Local residents were divided by the outbreak of the American Civil War, though a number enlisted into the Confederate States Army.

Several skirmishes took place in the county between federal and Confederate forces during 1863 and 1864, and a substantial number of slaves fled to federally-held territory to seek their emancipation.

Several towns that had prospered in the early 1900s were left totally abandoned,[21] and the vast majority of county residents were impoverished.

[23] Jim Crow racial segregation took hold after the close of the 19th century and persisted, depriving blacks of political and economic opportunities available to whites.

[24] In 1950, about one third of white residents had access to hot running water and flushing toilets, while no blacks had such amenities, and tended to live near small creeks and drainage canals.

[27] It has a flat topography and its highest point, a spot west of Alligator Lake, rests about 18 feet above sea level.

[13] Hyde County is within the path of the Atlantic Flyway, and thus features seasonal populations of various migratory waterfowl species, including tundra swan and Canada geese.

[39] There are no incorporated communities or municipal governments in Hyde; all local governmental activities occur at the county level.

According to the 2022 American Community Survey, an estimated 16.4 percent of county residents have attained a bachelor's degree or higher level of education.

[54] Historically, natives of both mainland Hyde County and Ocracoke Island often spoke a Hoi Toider dialect of English.

[55] The trend has declined over time, and, particularly since the 1970s, newer generations of local African Americans tend to speak a dialect closer to urban variants of African-American Vernacular English.