Santorum's withdrawal sets up what is sure to be an acrimonious seven-month fight for the presidency between Romney, the former Massachusetts governor, and Democratic President Barack Obama, with the certain focus on the still-troubled economy.
"This has been a good day for me," a smiling Romney told supporters in Wilmington, Del., saying he believes Santorum "will continue to have a major role" in the Republican Party.
In a preview of the personal attacks that lie ahead, Obama's campaign manager declared that Americans neither like nor trust Romney, and the Romney camp said the fight had always been about defeating Obama, not GOP rivals.
"This game is a long, long, long way from over," Santorum said as he bowed out of the contest with Romney. "We are going to continue to go out there and fight to make sure that we defeat President Barack Obama."
Santorum had been facing a loss in the April 24 primary in Pennsylvania, the state he represented in Congress for 16 years, and where the Romney campaign planned nearly $3 million in ads against him.
Whether or not there are lingering hard feelings, Santorum didn't mention Romney, who has been the front-runner for months and was far ahead in the race for the 1,144 delegates needed to clinch the nomination at the party's convention in August.
Romney has tried to ignore his GOP rivals and campaign against the president since he first entered the race last year with a pitch focused on the recovering but still frail economy. But Romney was forced to go after Santorum and former house Speaker Newt Gingrich after Santorum showed strength in Iowa and Gingrich in South Carolina early this year. Then Santorum kept on, memorably winning three Southern primaries.
Romney's campaign has long been the best funded, the best organized, and the most professionally run of the GOP contenders.
Despite Santorum's refusal to get out of the race earlier -- and Gingrich hasn't officially dropped out yet -- Romney had already begun looking ahead with a unifying message. He told Pennsylvania supporters last week that "we're Republicans and Democrats in this campaign, but we're all connected with one destiny for America."
And Obama has turned squarely to face Romney, recently assailing him by name, as his campaign has worked to paint Romney as a rich elitist who will win the nomination only because he buried his opponents under millions of dollars in negative advertising.
"Neither he nor his special interest allies will be able to buy the presidency with their negative attacks," Obama campaign manager Jim Messina said Tuesday after Santorum left the race. "The more the American people see of Mitt Romney, the less they like him and the less they trust him."
In response, a Romney campaign spokeswoman insisted that "for Mitt Romney, this race has always been about defeating President Obama, and getting Americans back to work."
But Romney still has had to wage a drawn-out nomination fight that's seen candidate after candidate try to block his path. That has highlighted Romney's problem with the most conservative voters. As recently as last week, activists huddled with Santorum to try and figure out how to keep him in the race, and Gingrich was still insisting Tuesday that his campaign represents the "last stand for conservatives" as he vowed to stay in the race until the convention.
Claiming a victory of sorts, Santorum said Tuesday, "Against all odds, we won 11 states, millions of voters, millions of votes."
That took its toll on Romney. It all started in Iowa, where vote counts initially showed an eight-vote Romney victory -- giving him momentum and headlines. But weeks later -- after the campaign had moved to South Carolina and Romney was battling Gingrich -- Santorum was declared the winner.
Romney's campaign left Santorum for dead as he beat Gingrich in Florida and won in Nevada. But he lost three states -- Colorado, Minnesota and Missouri -- to Santorum on Feb. 7, breathing new life into the former senator's insurgent candidacy and forcing Romney to compete for two more months. Santorum eventually won contests in Tennessee, North Dakota, Oklahoma, Kansas, Mississippi, Alabama and Louisiana.
The battle forced Romney to spend more money attacking Santorum with negative ads in big Midwestern states like Michigan, Illinois and Ohio, where he won increasingly large victories.
Now, he must rise to the daunting challenge of taking on an incumbent president backed by what's expected to be one of the most sophisticated re-election campaigns in history. Longtime Republican strategist Ed Gillespie joined the Romney campaign this month to help, but the team hasn't been able to expand much beyond the small core group of loyal strategists that waged the primary. The campaign will also need to ramp up the process to vet possible vice presidential picks.
"We'll be thinking about that this week and making a number of decisions," Romney said Tuesday after a supporter asked him who he might choose for his running mate.
Obama's campaign has a sizeable cash advantage over Romney's, having more than $84 million in the bank at the end of February, Federal Election Commission records show. Romney's campaign had about $7.2 million. Those filings show Romney has a fifth the paid staff of Obama's campaign. He had yet to tap the resources of the Republican Party that will become available to the party nominee.
Santorum's exit doesn't greatly change Obama's calculus. The president and his campaign have been expecting to face Romney all along and have already been targeting him. Yet the departure of Romney's chief GOP rival means this is the point where the Obama campaign will engage even more heavily.
From the White House, Vice President Joe Biden has led the political fire against Romney, and over the past week Obama has started tying his speeches about economic fairness to Romney -- directly, or in the coy way he chose Tuesday, warning of old, failed economic ideas from a candidate "who shall not be named."
Obama's speech in Florida, amid a full day of fundraising, was partly designed to draw a contrast between himself and Romney. The president is building his re-election campaign on the theme that he would help everyone succeed while Romney would cater to the rich and leave many people to struggle.
"This election will probably have the biggest contrast that we've seen maybe since the Johnson-Goldwater election, maybe before that," Obama told donors at a campaign event. In his 1964 race against Republican Barry Goldwater, former President Lyndon Johnson carried 44 of 50 states and won 61 percent of the popular vote, the largest share of any candidate since 1820.
Romney's team paints that argument as divisive. "This blame, this populism of trying to go and divide America, is not only wrong, it's dangerous," Romney said Tuesday in Delaware.
Romney trails Obama in organizing in some key battleground states such as Ohio and Florida, though Romney aides point to networks of supporters and volunteers that remain in place since his winning primary campaigns in the two electoral prizes.
The same is true in Iowa, where Romney nearly won the January caucuses, and New Hampshire and Nevada, where he did win in the primary campaign's early days. The five are in the top 10 most competitive since 2000, and were all carried by Obama four years ago.
Other more typically Republican-performing battlegrounds Romney is eyeing at returning to the GOP column include Colorado, Virginia and North Carolina, which Obama flipped after consecutive GOP victories.
So far, polling shows people tend to like Obama more than Romney. Yet the public's top issue is also Obama's biggest vulnerability. Despite recent improvements in the public's outlook, ratings of Obama's handling of the economy remain in negative territory. According to a Washington Post-ABC News poll released Tuesday, Romney and Obama are about even on which candidate Americans trust more to handle the economy.