Newberry County was formed from Ninety Six District in 1785. Prior to its formal founding, the area was the site of several American Revolutionary War battles: Williams' Plantation, Dec. 31, 1780; Mud Lick, March 2, 1781; and Bush River, May 1781. The town of Newberry was founded in 1789 as the county seat and was sometimes called Newberry Courthouse for that reason.
Originally settled by yeomen farmers, in the nineteenth century numerous plantations were established for the cultivation of short-staple cotton. Its processing had been made profitable by invention of the cotton gin. Cotton was the primary crop grown in Newberry County before the American Civil War, supported by the labor of enslaved African Americans, who comprised a majority of the population in the county. With numerous plantations yielding good revenue, planters formed the social elite of the county and city. Newberry was a trading town, and expanded with the arrival of the railroad in the early 1850s, which connected it to major towns and markets. Newberry College was established by the Lutheran Church in 1856.
The Civil War interrupted growth in the county; the warfare and loss of lives of many southern men disrupted the state economy. Emancipation of slaves after the war began to change the social order during Reconstruction. By the late 1870s, white Democrats had regained their political power in the state legislature. In the later 19th century, they passed a new constitution and other measures to disfranchise the blacks. White legislators passed Jim Crow laws enforcing racial segregation, which also lasted until the mid-1960s. This exclusion from politics lasted for most black residents until after the passage of civil rights legislation in the mid-1960s.
The first cotton mills were constructed in the county in the 1880s, and quickly became an important part of the economy and a source of jobs. For decades, jobs at the mills were limited to white workers. With the mechanization of agriculture in the early 20th century, labor needs were reduced. Many rural blacks left the county and state to migrate to northern and midwestern industrial cities for work during the Great Migration, which had two waves, before and after World War II. Less noticeable were rural whites who departed for opportunities in southern urban and suburban locations.