"We will continue to go out and fight and defeat President Barack Obama," Santorum declared.
Santorum spoke with Romney before the announcement, a Republican source close to the campaign said.
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 been hoping to hold out through the primary in Pennsylvania on April 24, but decided to fold up 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.
Santorum stressed the improbable accomplishment of the past year, saying that "against all odds, we won 11 states, millions of voters, millions of votes."
He said that while Romney was accumulating more delegates, "we were winning in a very different way. We were touching hearts" with his 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."