Scott Colom has won the Mississippi Senate race to become the first Democrat to win the seat in decades.
The last time a Democratic senator was elected in Mississippi was in 1982.
Mr Colom will now become Mississippi's first black US senator since the 19th century.
A majority of Mississippi voters said they disapproved of Donald Trump's overall job performance, citing both the US president's tariffs and the country's military action in Iran, according to NBC News exit polling.
The outlet reported that it had been a closely contested race between Mr Colom, a 43-year-old local prosecutor, and Republican incumbent Cindy Hyde-Smith, who was elected in 2018.
His victory, following a prolonged ballot counting process, means the Democrats will hold at least 55 Senate seats from January, with Alaska the only Senate race left to be called.
It comes after the party flipped a number of states from Republicans during the midterm elections to gain control of both chambers of Congress from next year.
In a video posted on social media, Ms Hyde-Smith conceded defeat and congratulated Mr Colom.
"While this is not the outcome we worked for or hoped for, I respect the decision of Mississippi voters," she said.
"I want to congratulate Scott Colom and wish him well as he takes on the tremendous responsibility of representing our great state."
Democratic leader Chuck Schumer celebrated the victory on social media, writing: "Scott Colom is the only person who could've gotten this done. I knew it from the moment I met him.
"Along with his staff and volunteers, Scott ran the campaign of a lifetime and re-imagined what's possible for Democrats in the South. He proved the polls, the pundits, and the prognosticators wrong at every turn."
During his election campaign, Mr Colom said that he could represent all of Mississippi - a state where racial divisions have long defined its politics and society.
"It's got to be about having a party that represents rural America again, suburban America, urban America - a party that makes sure we actually deliver for voters in ways that make their lives better, and we don't come up with excuses as to why we can't do it," he said.
Former President Bill Clinton, who campaigned with Mr Colom days before the election, said he had won "because you believe in the promise of your state's people. And they believed in you right back. I'm honored to have stood alongside you".
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(c) Sky News 2026: Democrat Scott Colom wins Mississippi Senate race
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