Darline Graham has been defeated by Democrat Annie Andrews in South Carolina, dealing a stinging blow to Donald Trump who handpicked the late Lindsey Graham's sister to run for the Senate seat vacated after his sudden death in July.
The Associated Press called the race for Andrews at 10.45pm.
Andrews had 51 percent to Graham's 47 percent with 86 percent of the vote counted.
Andrews' victory makes her the first Democrat to win a South Carolina Senate seat in 28 years and the first woman elected to represent the state in the chamber.
Trump, who carried the state by 18 points just two years ago, had thrown his weight behind Graham, campaigning for her during the primary runoff and returning twice in the closing weeks of the campaign.
But his intervention failed to save a candidate whose campaign was dogged by questions about whether she was equipped for the job.
Graham, who had never served in public office, made a series of gaffes during her campaign, admitting that she didn't have expertise in foreign policy, and even stating that she didn't know if she wanted to be a Senator.
At a Republican primary debate, Graham struggled with a question about Taiwan and the South China Sea before admitting: 'National security is not my thing.'
Andrews, who has never held elected office, turned that admission into an attack on Graham's fitness to serve a full six-year term.
Republican Darline Graham greets President Donald Trump at an October campaign rally in Pendleton
South Carolina Democratic Senate candidate Dr. Annie Andrews gets an update on election results from her campaign team while waiting with family before her victory
Andrews was seen hugging her mother, Marybeth Lintzenich, after receiving news of favorable election results
'If your surgeon said that appendectomies aren't really his thing, would you still hand him a scalpel? No,' Andrews said at their October 11 debate.
'So why would we hand Darline Graham a full term in the US Senate? She is unserious and unqualified.'
Andrews, who unsuccessfully challenged Representative Nancy Mace in 2022, focused her Senate campaign on affordability and economic concerns while portraying Graham as the choice of Washington insiders.
She also sought to blunt Republican attacks casting her as too liberal for South Carolina, criticizing both parties' handling of immigration and stressing her support for gun rights, border security and lower taxes for the middle class.
The surprisingly competitive contest drew national Republican money into a state the party had long considered safe, with the GOP committing $5 million to bolster Graham as the race tightened.
Andrews' victory was powered by strong performances in deep-red rural counties that Graham felt she could count on.
The candidates also clashed over Graham's decision to campaign without her married surname, Nordone.
Andrews suggested her opponent had recently changed her name, an accusation Graham rejected.
'My legal name is Graham and has always been Graham,' she said. 'And you know why it's Graham? Because I lost my parents when I was a little girl, and I kept the name Graham so that I felt connected to them.'
After a brutal evening, in which Republicans lost control of both the House and Senate, Trump insisted that they would have won by a landslide if he had been on the ballot and seemed to blame the candidates themselves.
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