Speaking at a victory party at the Embassy Suites in downtown Orlando, Nelson said he was thankful for the support of Florida voters.
"I want you to know, in the toxic atmosphere that you've seen, Connie Mack is my opponent. Not my enemy," said Nelson.
One of Nelson's last campaign stops Monday was on an Orlando street corner in the very way and on the very spot he launched his first run for the Florida House in 1972. Clutching a sign that read "Hi, I'm Bill Nelson," he and his wife waved to supporters in their cars.
Forty years later, the veteran politician said he didn't take his successes for granted and fought a contentious battle with Republican rival Connie Mack IV.
Nelson said Tuesday night he pledged to end partisan gridlock.
The 70-year-old Nelson won even though he was up against the son of Florida's former U.S. Senator. Mack is also named after his great-grandfather, a baseball Hall of Famer.
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.
WATCH: Mack concedes
Standing side by side with his family and friends, Mack conceded the race in Bonita Springs. His father, former Senator Connie Mack, introduced him and congratulated him on the race he ran.
"It's not whether you win or lose but how you play the game," said the senior Mack.
Rep. Mack called Senator Bill Nelson on the phone to congratulate him before taking the stage. Mack had trailed Nelson in the polls coming into Tuesday but was hopeful and confident he could win the seat his father once held.
Mack said he was proud of the way he ran and stood firm to his convictions.
"This is not a sad moment, it is an inspiring moment. This is what America is. We went through the battle of a campaign. We fought hard to win. We didn't win, but we continue to fight for the ideas and beliefs we have always believed in," said Mack.