The victory continues Nelson's 40-year political career and ends, for now, the political career of Mack. He had been representing southwest Florida in Congress.
Nelson portrayed himself as a moderate during the campaign while Mack tried to tie Nelson to President Barack Obama by noting his votes for the stimulus and health care overhaul.
Democrats currently hold a 53-47 edge in the Senate, including the two independents who caucus with them. Republicans need a net of four seats to grab the majority, three if Republican Mitt Romney wins the presidency.
Around the country
Independent Angus King captured a Republican-held Senate seat in Maine on Tuesday, adding a dose of uncertainty to the fight between majority Democrats and the GOP for control of the Senate.
King prevailed over Republican Charlie Summers and Democrat Cynthia Dill in the race to replace Republican Sen. Olympia Snowe, who blamed partisan gridlock in Washington for her unexpected decision to retire after 18 years in the Senate. The Associated Press called the race based on interviews with voters as they left polling stations.
In Connecticut, Democratic Rep. Chris Murphy won the seat held by Sen. Joe Lieberman, the independent who was the Democratic Party's vice presidential nominee in 2000. Murphy's win marked the second straight defeat for former wrestling executive Linda McMahon, who spent $50 million of her own wealth in a failed effort against Sen. Richard Blumenthal in 2010 and more than $42 million this election cycle.
Independent Sen. Bernie Sanders won a second term in Vermont. Democratic Sens. Sheldon Whitehouse in Rhode Island, Ben Cardin was in Maryland and Tom Carper in Delaware were all re-elected. Tennesseans gave Republican Sen. Bob Corker a second term.