CNN, USA Today and The Wall Street Journal, as well as the major TV networks, projected Romney the victor.
In his victory speech, Romney told a cheering crowd Democrats expect the bruising primary campaigns will result in a weakened GOP nominee, but he said that won't happen.
"A competitive primary does not divide us, it prepares us, and we will win," Romney said.
"Ours will be a united party with a winning ticket for America" when the GOP convention is held in Tampa, Fla., the week of Aug. 27, he said.
Second-place finisher Newt Gingrich, speaking to his supporters in Florida, assured them he will remain in the race.
"It is now clear that this will be a two-person race between the conservative leader, Newt Gingrich, and the Massachusetts moderate," he said.
"We are going to contest every place and we are going to win and we will be in Tampa as the nominee in August," Gingrich said.
"We're going to have people power defeat money power in the next six months."
U.S. Sen. Marco Rubio, R-Fla., said before the votes were counted he thinks Florida is the true bellwether state.
"I think the winner of Florida is in all likelihood going to be the nominee of our party," Rubio told CNN. "Florida is a mini America."
Gingrich supporters who gathered at an Orlando hotel to await the outcome were quieted by the results, but there were vows to soldier on toward the remaining primaries, the Los Angeles Times reported.
"I expected him to win," said Marilyn Butler, 65, of Orlando. "And we'll keep working till he's the nominee."
The Florida Secretary of State's Web site gave the former Massachusetts governor 772,470 votes to 531,808 (31.94 percent) for former U.S. House Speaker Newt Gingrich of Georgia.
Former U.S. Sen. Rick Santorum of Pennsylvania was a distant third with 222,482 votes (13.36 percent) and U.S. Rep. Ron Paul of Texas was fourth with 116,888 votes (7.02 percent).
Several other GOP candidates and former candidates polled less than 1 percent, as Florida Republicans cast their votes to determine who will get the state's 50 delegates to the convention.
Santorum said the key message coming out of Florida is that Republican candidates need to do a better job of concentrating on issues the rest of the primary campaign season.
"Let's focus on the real issue, which is defeating Barack Obama. We're not going to do that by mudslinging," Santorum said.
He said Republicans need a candidate who can "draw a clear contrast" with President Barack Obama on healthcare, trade, Wall Street "and the bailouts … approved of by Newt Gingrich and Mitt Romney." He said he would deliver a speech in Nevada Wednesday on "Romneycare and Obamacare."
Paul, who spent little energy or money trying to make inroads in Florida, told his cheering supporters he had called Romney to congratulate him.
"But I also said I would see him soon in the caucus states," the libertarian-leaning congressman said. "Something big is happening in this country and it's all very favorable. People are beginning to realize that the problem is too much government. We need more personal liberty.
"And this is where we're winning the hearts and minds of people."
Romney had led the GOP field in many pre-primary polls, as Gingrich came under a barrage of criticism from Romney, who had prevailed in New Hampshire and was a close second in Iowa.
Gingrich's campaign said Monday it planned to win enough delegates in the coming months to force a brokered convention.
At a precinct in Pembroke Pines Tuesday, one voter said Romney was the candidate with "the total package" who had it all over Gingrich, the South Florida Sun Sentinel reported.
"I can't vote for anyone without any ethics," Mirta Chediak told the newspaper.
A voter in Fort Lauderdale, however, said he supported Gingrich because he is a "people person."
"He can relate to general people while Mitt Romney is on his own little planet," Jerry Jordan said.