As Attorney General of South Carolina, Wilson has litigated to block same-sex marriage, invalidate the Affordable Care Act, challenge environmental regulations, defend anti-abortion laws, and prohibit masking and vaccine requirements.

[2] His mother, Roxanne Dusenbury McCrory, later married Joe Wilson, who currently serves as the U.S. representative for South Carolina's 2nd congressional district.

[4] Wilson graduated from Francis Marion University, where he joined the Pi Kappa Alpha Fraternity through the Theta Delta chapter, with a bachelor's degree in political science[1] in 1996, and received a J.D.

In the contentious Republican primary, Wilson faced two challengers for renomination, state Representative Todd Atwater and attorney William Herlong of Greenville.

[10] Both challengers focused on ethics issues, criticizing Wilson for his connections to the Quinns, who reached a plea deal after being embroiled in a Statehouse corruption investigation.

In February 2013, Wilson originally admitted his campaign failed to disclose and report receiving at least 15 separate contributions of unknown amounts.

[16] In 2014, Wilson asked the South Carolina Supreme Court to block the issuance of marriage licenses to same-sex couples in the state.

[25] After Harrell pleaded guilty to misusing campaign money and resigned from the House in late 2014, Pascoe emailed the attorney general's office, urging the Quinns be investigated.

[25][29] Pascoe challenged Wilson's attempt to fire him, arguing that the attorney general could not do so after previously recusing himself on the grounds of a conflict of interest.

[28] In July 2016, the South Carolina Supreme Court sided with Pascoe on a 4–1 decision, rejecting Wilson's attempt to fire him as special prosecutor.

[25] In October 2018, after a two-year investigation, a state grand jury issued a 270-page report on corruption in South Carolina, including blurred relationships between businesses, legislators, lobbyists, and political consultants.

[33] In 2021, Wilson joined a Republican lawsuit challenging President Biden's order directing federal agencies to consider the costs of greenhouse gas pollution in making decisions.

[43] The next month, in advance of the January 6 attack on the United States Capitol by a pro-Trump mob, the Republican Attorneys General Association, then chaired by Wilson, made robocalls encouraging "patriots" to march on Washington and demand that Congress overturn the election results and keep Trump in power.

[42][44] He said he was "completely unaware" of the Republican Attorneys General Association robocalls; the group's executive director, a former Wilson aide Adam Piper, resigned.

[46] In August 2021, ahead of the start of the 2021–2022 school year and amid an increasing number of COVID-19 cases in the state, Wilson said that the University of South Carolina could not implement indoor mask requirements for campus access.

Wilson contended that a proviso (a type of state budget measure) passed by the General Assembly earlier that year prohibited such a mandate.