(CNN) -- With a decisive win in the Illinois presidential primary, former Massachusetts Gov. Mitt Romney sets his sights on the bayou where Louisiana holds the next Republican primary.
"We thank the people of Illinois for this extraordinary victory," Romney told supporters in the Chicago suburb of Schaumburg. "Elections are about choices. Today, hundreds of thousands of people in Illinois joined millions of people in this country in this cause."
With 99% of precincts reporting, Romney led former Pennsylvania Sen. Rick Santorum by a 47%-to-35% margin. Texas Rep. Ron Paul was running third at 9%, while former House Speaker Newt Gingrich had 8%.
With the victory, Romney was poised to win at least 41 of the 54 delegates up for grabs in the state, giving him a total of 562, according to CNN's estimate. Santorum is second with 249, Gingrich third with 137 and Paul last with 69.
A total of 1,144 delegates are needed to clinch the GOP nomination.
Louisiana will hold its primary on Saturday.
The victory led several observers to question whether the remaining GOP field can deny Romney the chance to carry the party's standard against President Barack Obama in November.
Romney "hasn't definitely won," CNN political analyst David Gergen said. "But in a campaign that has had many, many unexpected twists and turns, I think we may look back tonight and say tonight was the final big turning point.
"Here in a big state, Newt Gingrich has faded as a candidate," Gergen said. "Santorum had a chance to go one-on-one against Romney, in effect, and Santorum somehow has gone off the rails in his campaign."
Santorum has made a series of high-profile gaffes in the past week, saying Spanish-speaking Puerto Rico needs to adopt English as its principal language to become a U.S. state, and saying Monday that the unemployment rate "doesn't matter to me." Romney's campaign jumped on the remark, but Santorum said that "of course" he cared about joblessness -- but his candidacy was "about freedom."
Santorum skipped Illinois on primary night and awaited the results in Gettysburg, Pennsylvania. In his concession speech, below a banner that proclaimed "Freedom," he said he was staying in the race to battle a government he said is "trying to order us around."
"This is an election about fundamental and foundational things," Santorum said. "This is an election about not who's the best person to manage Washington or manage the economy. We don't need a manager, we need someone who's going to pull government up by the roots and do something to liberate the private sector in America."
In Illinois, he led among blue-collar voters, in rural areas and among those who considered themselves "very conservative," according to the exit polls. But the surveys showed Romney leading heavily among the more than 50% of voters who ranked the economy as the No. 1 issue in the campaign. And among the 37% who considered the chances of beating President Barack Obama in November their top quality in a candidate, three-quarters said they were voting for Romney.
Gingrich, meanwhile, issued a statement blasting Romney for relying on his vast financial resources rather than offering "solutions that hold the president accountable for his failures."
"To defeat Barack Obama, Republicans can't nominate a candidate who relies on outspending his opponents 7-1," Gingrich said.
But Romney campaign spokeswoman Andrea Saul said, "That's like a basketball team complaining they lost to another team because their players were too tall."
"Fundraising is part of a campaign. So is organization," she said.
State Treasurer Dan Rutherford, Romney's Illinois campaign chairman, said it's time for the rest of the field to start thinking about bowing out.
"My state has already gone to bed now," Rutherford said in a statement. "We've already put this in the bank. I think that it's about time some of these candidates step back and say what's the best interest for the nominee to be able to take on Barack Obama and the White House, and when is it they need to say 'OK, I gave it my best shot, and now let's move to the next chapter in our lives.' "
But Santorum spokesman Hogan Gidley said his candidate plans to continue campaigning in upcoming contests in Louisiana, Wisconsin and North Carolina.
"Some of these states who typically are force-fed an establishment nominee at this point are getting to see the campaign up close and personal," Gidley said. "They're going to get to see Speaker Gingrich. They're going to get to see Mitt Romney. They're going to get to see Rick Santorum. We'll see, as we move into the convention, just who people are gravitating behind."
Santorum advisers were putting out the word that they were planning to fight for the nomination on the floor of the Republican convention in Tampa if necessary.
"We do acknowledge that it's difficult for any candidate to get to a majority prior to the national convention," Santorum delegate director John Yob said. "If this race goes to the floor of the national convention, we view that at as favorable terrain for Santorum because the delegates to the national convention will by and large be more conservative than the primary voters who voted in the binding contests."
Gingrich and Paul plan to head into Louisiana, which holds its GOP primary Saturday. But CNN analyst Erick Erickson, a longtime Romney critic, said "the writing's on the wall" for the rest of the field.
"This comes down to Mitt Romney," Erickson said. "Not only is he the front-runner, but the nominee. This is a clear win for Mitt Romney tonight in a state with blue-collar voters, with industrial voters and suburban voters."
Romney's win further pads his estimated lead. But for the former Massachusetts governor, who has struggled to win over the conservative GOP base, a clear popular-vote win might be just as important.
He finished third in Alabama and Mississippi primaries a week ago, behind Santorum and Gingrich. But unlike the Deep South states, Illinois has a large, somewhat moderate GOP electorate concentrated around Chicago.
Romney regained a bit of momentum on Sunday when he trounced Santorum in Puerto Rico's primary. He got 83% of the vote, picking up all 20 delegates at stake, and cutting back on time in Puerto Rico to make weekend stops in Illinois. He also dropped his emphasis on the math that he argued made it clear that he alone has the only shot during the primary and caucus season to clinch the nomination.
Over the past few days, he appeared to be increasing his attention to female voters and to gas prices, as well as touting his business credentials and suggesting Santorum would be an "economic lightweight." In response, Santorum asked if Americans wanted a president with ties to big banks.
"I heard Gov. Romney here called me an 'economic lightweight' because I wasn't a Wall Street financier like he was. Do you really believe this country wants to elect a Wall Street financier as the president of the United States?" Santorum asked at a campaign rally in Rockford.
CNN's Paul Steinhauser, Kevin Bohn and Phil Gast contributed to this report.