The district spans from Columbia to the South Carolina side of the Augusta, Georgia metropolitan area.

The district's current configuration dates from 1933, following South Carolina losing a seat in apportionment as a result of the 1930 Census showing that the state's population had declined.

In a deal between Republicans and Democrats, the 6th district, previously located in the northeastern portion of the state, was reconfigured to incorporate most of the old 2nd's black residents.

After white Democrats regained control of state governments across the South, in the late 19th century, they passed new constitutions from 1890 to 1908 to disenfranchise blacks, excluding them totally from the political process.

The district swung hard to Strom Thurmond during his third-party bid for president in 1948, and gave an equally massive margin to Barry Goldwater in 1964.

In the most recent election, held on November 11, 2022, Wilson earned 60% of the vote against Democrat Judd Larkins.