Historically, the "eastern Siouans" had territories extending through the area of Columbus County prior to any European exploration or settlement in the 16th century.

Following epidemics of new infectious diseases, to which indigenous peoples were exposed in trading and other contact, the Waccamaw and other Native Americans often suffered disruption and fatalities when caught between larger tribes and colonists in the Tuscarora and Yamasee wars.

William Bartram, a botanist from Pennsylvania, journeyed to Lake Waccamaw to study the flora and fauna of the region in the 1730s, creating the first detailed written account of the area.

[4] At least two skirmishes of the American Revolutionary War were fought on Columbus soil: one near Pireway and another at Brown Marsh.

[10] Most white men in the county fought during the American Civil War, while most free blacks and mulattoes were exempted from service.

The county was spared direct fighting, but the war demands stressed the local labor and food markets, and severe rains in 1863 diminished grain yields.

[11] After the war Columbus' economy grew more heavily reliant on corn and cotton production.

Toward the end of the century, the U.S. Census recorded common Waccamaw surnames among individuals in the small isolated communities of this area.

[5] In 1950 Thomas Hamilton, a South Carolina leader of a white supremacist Ku Klux Klan chapter, began a recruiting campaign to expand his organization's reach into Columbus County, focusing on the towns of Chadbourn, Fair Bluff, Tabor City, and Whiteville.

[17] In late July they paraded through Tabor City, passing out handbills which exhorted white men to join them in resisting "Jews, nigger, and integrationist quacks".

[20] The following January the Klansmen began night raids on homes, abducting and flogging residents who they felt had violated traditional mores.

[21] In early October 1951 Klansmen from Fair Bluff abducted a couple and transported them into South Carolina.

[22] In February 1952 the FBI, state agents, and county sheriff's deputies initiated a crackdown and arrested 11 Klansmen responsible for the October abduction.

[22] For their efforts against the Klan, in 1953 the Tabor City Tribune and The News Reporter won the Pulitzer Prize for Public Service.

[23] By the early 1980s, Columbus County had a reputation for intense political competition marked by accusations of fraud and impropriety.

[24][25] The FBI had received several complaints from local police officers and residents about alleged protection rackets run by public officials and election fraud.

In early 1980, a former FBI informant moved to the county and reported that he was being told to pay bribes to ensure the smooth operation of his business.

[26] Taking into account the previous complaints they had received, upon being informed, the FBI initiated an undercover investigation into corruption in Columbus County, codenamed "Colcor".

[26] The agents also paid bribes to county commission chairman Ed Walton Williamson in exchange for political influence.

[27] With Williamson's help, the agents devised a scheme to investigate election fraud by instigating a referendum in the town of Bolton to legalize liquor-by-the-drink and supplying a local political leader with funds to buy votes to achieve their desired outcome,[28][29] the first time the FBI had ever tried to manipulate a public election.

The area contains the Brown Marsh Swamp, and has a remnant of the giant longleaf pine forest that once stretched across the Southeast from Virginia to Texas.

[51] The county is a member of the regional Cape Fear Council of Governments, where it participates in area planning on a variety of issues.

[54] There are two state prisons within Columbus County:[55] In November 2022, Sheriff Jody Greene was re-elected to office after resigning several weeks prior due to allegations of obstructing justice and racism.

After the Reconstruction era, Columbus County's politics fell under the domination of the Democratic Party.

Through much of the 20th century, local primaries were the preeminent political contests, marked by intense intraparty competition.

Following the election of Democrat Barack Obama as U.S. president in 2008, Republicans' performance in local races markedly improved.

[65] The North Carolina Department of Commerce classifies the county as economically distressed[66] and it has regularly suffered from a higher unemployment rate than the state average.

[70] According to the 2021 American Community Survey, an estimated 14.1 percent of county residents have attained a bachelor's degree or higher level of education.