"We made a decision over the weekend, that while this presidential race for us is over, for me, and we will suspend our campaign today, we are not done fighting," he said.
Santorum, appearing with his family, told supporters that the battle to defeat President Barack Obama would go on but he pointedly made no mention or endorsement of Romney, whom he had derided as an unworthy standard-bearer for the GOP.
The former Pennsylvania senator stressed that he'd taken his presidential bid farther than anyone expected, calling his campaign "as improbable as any race that you will ever see for president."
"Against all odds," he said, "we won 11 states, millions of voters, millions of votes."
Santorum signaled his intention of maintaining a voice in the campaign to come, saying: "This game is a long, long, long way from over. We will continue to go out and fight and defeat President Barack Obama."
Santorum spoke with Romney before the announcement, a Republican source close to the campaign said, and Romney asked to meet him sometime in the future
The delegate totals told the tale of Santorum's demise. Romney has more than twice as many delegates as Santorum and is on pace to reach the 1,144 needed to clinch the nomination by early June. Still in the race, but not considered a factor: former House Speaker Newt Gingrich and Texas Rep. Ron Paul.
Santorum had hoped to keep his campaign going through the Pennsylvania primary on April 24, but decided to fold after his severely ill 3-year-old daughter, Bella, spent the weekend in the hospital.
Santorum, a feisty campaigner who took everyone by surprise with his win in Iowa's leadoff caucuses, ran on his conservative credentials and his experience in Congress - he was a House member for four years and senator for 12 - but was hobbled by a lack of money and organization.
He said that while Romney was accumulating more delegates, "we were winning in a very different way. We were touching hearts" with a conservative message.
In a statement, Romney called Santorum "an able and worthy competitor" and congratulated him on his campaign.
"He has proven himself to be an important voice in our party and in the nation," Romney said. "We both recognize that what is most important is putting the failures of the last three years behind us and setting America back on the path to prosperity."
Santorum said the campaign had been "a love affair for me, going from state to state. ... We were raising issues, frankly, that a lot of people did not want raised."
He spoke almost nostalgically of the race, and of his trademark sweater vest, a pointed visual contrast to his suited rivals.
"Over and over again we were told, 'Forget it. You can't win,'" he said.
Eventually, the improbable had to bow to reality: Santorum would have needed 80 percent of the remaining delegates to win the nomination before the party's national convention in Florida in August. And that couldn't happen as long as Romney was in the race because most upcoming primaries use some type of proportional system to award delegates, making it hard to win large numbers of delegates in individual states.
In most states, Santorum's delegates can now support any candidate they choose.
Gingrich, who has been splitting the votes of those who questioned Romney's conservative credentials with Santorum, made an immediate play for his supporters.
He said the former senator's campaign was "a testament to his tenacity and the power of conservative principles.
"I am committed to staying in this race all the way to Tampa so that the conservative movement has a real choice. I humbly ask Senator Santorum's supporters to visit Newt.org to review my conservative record and join us as we bring these values to Tampa."
Paul also congratulated Santorum for "running such a spirited campaign" and called himself "the last - and real - conservative alternative to Mitt Romney."
Suspending the campaign allows Santorum to keep paying off nearly $1 million in debt, according to recent Federal Election Commission filings. Those debts include about $500,000 for media consulting and tens of thousands more for telemarking and online advertising, records show.
Other presidential candidates have eventually extinguished their debt and terminated their campaigns. Former Minnesota Gov. Tom Pawlenty officially shuttered his campaign committee on Tuesday, owing as much as a half a million dollars last fall but slowly whittling that figure down.
Associated Press writers Kasie Hunt, Jack Gillum and Nancy Benac in Washington contributed to this report.