Republican South Carolina Senate candidate Darline Graham is projected to have lost her race, handing Democrats their first victory in the state for 28 years.
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.
Graham was appointed to fill the seat in July after the sudden death of her brother, Senator Lindsey Graham, a move that won support from President Donald Trump.
A political newcomer, she conceded during the primary that she was "not that informed on national security".
LIVE RESULTS: Follow live results as they come into the BBC
ANALYSIS: Democrats eye sweeping gains and reshaping of political map
Trump won the state by 18 points in 2024.
During her primary campaign, Graham acknowledged her lack of political experience, particularly after stumbling on 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.
Darline Graham wins primary to contest late brother's US Senate seat
US senator and close Trump ally Lindsey Graham dies after 'brief and sudden illness'
BBC asks voters across US what brought them to the polls today
EXPLAINED: Why Trump's approval rating matters in the midterms
IN DEPTH: The Republicans walking a Trump tightrope
RESULTS: Who will win the midterms? How the US elections will be won and lost
Voter voices: Trump's influence on US midterm voters
Fox Style News Syndicate. Sourced from broadcast reporting: Read Full Source Coverage.