Hyde-Smith's victory, coming after her comments about joining a supporter on the front row of a public hanging, bolsters the Republican majority in the Senate and illustrates President Donald Trump's ability to rally his supporters behind a struggling campaign.
Hyde-Smith was also helped by an election eve visit by President Trump, who held two rallies with her on Monday.
"We have worked very hard, and we feel very good", Hyde-Smith said.
With 76 percent of precincts reporting, Hyde-Smith led with 56 percent of the vote, to 44 percent for Espy.
Cindy: 'I guess what I'm really saying is F*** Hyde-Smith and anyone who voted for her.
The AP has called the runoff for Hyde-Smith, more or less officially putting a cap on the evening. She initially called the public hanging remark "an exaggerated expression of regard".
He campaigned for her during her Senate runoff against Democrat Mike Espy.
"While we are hopeful that the Senator-elect will prove herself worthy of her new office, this election demonstrates the need to continue broadening the tent of civic and democratic participation in our nation", the pioneering civil rights organization said in a brief statement.
Unai Emery will be without four players for the trip to Bournemouth
In an interview with Spanish media outlet Marca, Arsenal head coach Emery said: "I met once with him, and little else". We had dinner with him on Wednesday and his energy and passion is infectious".
The remarks highlighted the racist lynchings that marred Mississippi's history, a fact her opponent was quick to point out.
Democrats had hoped a surge in turnout among black voters - who make up almost 40% of Mississippi's population, the largest share in the nation - could carry Espy to victory in a state that is highly polarized along racial lines, with most white voters backing GOP candidates and black voters supporting Democrats. The 64-year-old Democrat previously served in the House of Representatives for six years before going on to serve as President Bill Clinton's secretary of agriculture from 1993 to 1994.
Hyde-Smith, who was appointed to the Senate earlier this year after GOP Sen.
U.S. Senator Cindy Hyde-Smith (R-MS) waves to supporters after speaking during an election night event at The Westin Hotel, November 27, 2018 in Jackson, Mississippi. And it was revealed that she'd attended a private high school that was created to avoid desegregation - and sent her daughter to one as well.
"While this same-sex couple's request for a permit to utilize one of our state's facilities for a "commitment ceremony" is not being defined as a marriage ceremony, it is personally troubling for me", she said at the time, citing her "personal and religious beliefs". But if black voters rise to 40 percent of the electorate and Espy wins 9 out of 10, he needs less than a quarter of white votes for victory.
Her win on Tuesday means Republicans will hold 53 seats to Democrats' 47 seats in the Senate in January.
Hyde-Smith apologized for her "public hanging" comment, which she maintains was made in jest.
Espy resigned the Cabinet post in 1994 amid a special counsel investigation that accused him of improperly accepting gifts.