Republican South Carolina Senate candidate Darline Graham is projected to have lost her race, handing Democrats their first statewide victory in 28 years.
The Democrat, Annie Andrews, a former paediatrician, was on course to pull off a stunning upset in Tuesday's midterm elections, according to the BBC's US partner CBS.
With President Donald Trump's blessing, Graham was appointed to fill the seat in July after the sudden death of her brother, Senator Lindsey Graham.
But the political newcomer conceded during the primary that she was "not that informed on national security".
Trump won the state by 18 points in 2024.
During her primary campaign, Graham acknowledged her lack of political experience, particularly after stumbling during a foreign-policy question during a recent debate.
Asked about the US stance towards Taiwan, Graham had said: "National security is not my thing, not my area of expertise, but I do support the military."
Her brother, Lindsey Graham, was elected to the Senate in 2002 and was one of Washington's most influential voices on foreign policy, often pushing for US military intervention overseas.
