[5] The town's name refers to the free-flowing springs that merge into a stream and small lake surrounded by large, mature holly trees.

[citation needed] The Tuscarora Indians used the area around Holly Springs as a hunting ground prior to colonial settlement.

By 1800, the crossroads had spawned a village, including a general store built by Richard Jones, a Baptist church, and a Masonic lodge.

[10] Holly Springs Academy opened its doors in 1854 to prepare young men for admission to Wake Forest College.

Captain Oscar R. Rand recruited willing men of all ages to join Governor Zebulon Baird Vance's 26th Infantry Regiment in the Confederate States Army.

Bands of marauding robbers known as "bummers" raided the area farms and homesteads, taking food, supplies, silver, clothes, and anything of value.

Also during the war, for a two-week period, a segment of the Union Army encamped near Holly Springs and set up headquarters in the Leslie-Alford-Mims House.

The exodus was encouraged by construction of the Chatham Railroad through the village of Apex, giving that neighboring town a link to the outside world, which Holly Springs did not have.

In 1875, George Benton Alford moved his successful mercantile business from Middle Creek Township to Holly Springs, and was instrumental in beginning an economic revival in the community.

[14] Alford, a businessman and politician, started several businesses, including a mercantile store, a sawmill, a cotton gin, and the Holly Springs Land and Improvement Company, and eventually, the General Assembly granted the town a charter.

He also got other prominent men in the community to join him in seeking a charter of incorporation for the Cape Fear and Northern Railroad, which became the Durham and Southern Railway.

Under the leadership of Raymond A. Burt, J. Carter, and the Women's School Betterment Association, 10 acres (40,000 m2) near the springs were purchased (this was, in time, the site of the library and cultural arts center).

[citation needed] The town's population had not increased a great deal, holding at around 300, but the business community and the schools were drawing outsiders.

During the early 1960s, with a population stabilized at around 580, the town installed fluorescent streetlights about the same time that Highway 55 (Main Street) was widened.

[16] During this period, the town hired Dessie Mae Womble, the first black female chief of police in North Carolina.

As segregation gave way to integration, the Holly Springs School for Blacks was closed, and many of its students were sent to surrounding communities to further their educations.

[17] On July 18, 2006, pharmaceutical company Novartis announced it would be building a manufacturing facility in Holly Springs and employing about 350 to produce flu vaccines using new technologies.

When the company decided not to locate on the site, the Wake County Board of Commissioners voted five to two to proceed with plans to build a landfill there.

[19][20] For years, town leaders have become increasingly confident that Holly Springs is positioned to experience high growth, propelled by the economic engine of Research Triangle Park (RTP).

On April 16, 2011, a large tornado touched down close to the Holly Springs town center, uprooting trees and destroying homes and buildings.