"We have a ways to go, but we are getting close," McCain told his cheering supporters.
Stressing his aspiration to follow in the footsteps of former President Ronald Reagan, McCain sought to further bolster his credentials among Republican voters.
"It shows one thing. I'm the conservative leader who can unite the party," the Arizona senator told the Associated Press of his Florida victory.
The Florida vote was also one of the first where those casting ballots had to be registered party members, making it one of the first closed primaries to fully test the support of party faithful -- a group that McCain had struggled with in the past.
"This win in a closed primary will do a lot to cement John McCain in the eyes of a lot of people as the frontrunner," Chris Cillizza of Washingtonpost.com said. "It puts him in the driver's seat going into Super Tuesday."
According to AP exit polls, Florida Republican voters were split based on ideology, with McCain winning 4 in 10 moderates and Romney winning 4 in 10 conservatives.
"We are seeing a fracture emerge in the Republican Party," Stuart Rothenberg of the Rothenberg Political Report told the NewsHour Tuesday night. "McCain keeps winning the same kind of voters, but he did attract enough conservatives to put him over the top."
For former New York City Mayor Rudy Giuliani, who had campaigned heavily in Florida for weeks ahead of Tuesday's vote and spent some $3 million in advertising in the state, a third-place performance appeared to spell the end of his campaign.
Giuliani garnered some 15 percent of the vote and when he spoke to his supporters he notably used the past tense to discuss his campaign.
"We ran a campaign that was uplifting," Giuliani said Tuesday night in Orlando, Fla. "Win or lose our work is not done, because leaders dream of a better future and then work to bring it into reality."
By 10p.m. EST, as McCain spoke with his supporters in Miami, news organizations began reporting that Giuliani would drop out of the race on Wednesday and throw his support to McCain.
The results were also a major blow to the Romney camp, which had led in Florida until the final days of the campaign, when several key Republican officials publically backed McCain.
In the lead-up to the Florida vote, Romney and McCain had taken sharper aim at one another.
Romney blasted McCain for pushing campaign finance reform, his support of President Bush's immigration reform bill and his backing of an energy bill that he said would have driven up consumer costs.
"If you ask people, 'look at the three things Senator McCain has done as a senator,' if you want that kind of a liberal Democrat course as president, then you can vote for him," Romney told campaign workers. "But those three pieces of legislation, those aren't conservative, those aren't Republican, those are not the kind of leadership that we need as we go forward."
In conceding defeat, Romney repeated his accusation that the national political system was "broken" and his campaign would change this.
"We are not going to change Washington by sending the same people back just to sit in different chairs. I think it is time for the politicians to leave Washington and for the citizens to take over," Romney told cheering supporters in St. Petersburg, Fla.
For former Arkansas Gov. Mike Huckabee, a fourth place finish appeared to do little to dampen his long-shot campaign for the presidency.
"We are playing all nine innings of this ballgame," Huckabee told supporters in Missouri. "I am not sure everybody is going to be there," Huckabee said in a thinly veiled swipe at Giuliani, "but I am sure going to be there."
On the Democratic side, Sen. Hillary Clinton hoped to get a largely public relations boost from receiving the most votes in the devalued Democratic primary. The national party stripped the state of all of its delegates for moving up its primary date and the candidates agreed to not actively campaign in the state.
That said, Clinton arrived in the state Tuesday to thank her supporters. She had been leading in the state by 20 points in most polls and campaign officials had hoped the vote would give her a boost following the drubbing they took in South Carolina on Saturday.
Clinton appeared in front of a raucous room of supporters outside Fort Lauderdale, thanking them "for their vote of support," adding she would push for the full complement of 185 delegates to be seated at the convention.
Obama, who said he would not campaign in Florida, attempted some humor to respond to the news of Clinton's victory.
Bill Burton, spokesman for Obama, sent out an email to media under headline "Breaking...", "Obama and Clinton tie for delegates in Florida. 0 for Obama, 0 for Clinton."