[5] The name is of unknown origin, although one theory suggests that it was named by Quaker settlers in honor of their home of Newberry, a suburb of London in the United Kingdom.

Prior to its formal founding, the area was the site of several American Revolutionary War battles: Williams' Plantation, December 31, 1780; Mud Lick, March 2, 1781; and Bush River, May 1781.

Originally settled by yeomen farmers in the 19th century, numerous plantations were established for the cultivation of short-staple cotton.

Cotton was the primary crop grown in Newberry County before the American Civil War.

The Civil War interrupted growth in the county; the warfare and loss of lives of many southern men disrupted the state economy.

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.

At the 2010 census, there were 37,508 people, 14,709 households, and 10,129 families living in the county.

[17] At the 2000 census,[18] there were 36,108 people, 14,026 households and 9,804 families living in the county.

Newberry County has served as a reliable bellwether for South Carolina through the 20th century, having voted for the statewide presidential winner in 17 straight elections since 1956.

[21] As of April 2024[update], some of the largest employers in the county include Caterpillar Inc., Georgia-Pacific, Komatsu Limited, Kraft Foods, Newberry College, Samsung Electronics, Valmont Industries, and Walmart.