"Our campaign is making history," Santorum said in an e-mail to supporters moments after he was projected the winner of this southernUSstate by US media.
The race was called after the formerPennsylvaniasenator established a strong 50-percent lead, with Romney trailing far behind with 26 percent of the vote.
Former House speaker Newt Gingrich was third with 16 percent of the ballot and Texas Representative Ron Paul had six percent.
Written off early on in the campaign, Santorum has steadily notched up wins now 11 out of 34 contests -- largely with the help of evangelical Christians and the party's most conservative members.
"Not since Ronald Reagan in 1976 has a conservative candidate won as many states as we have," Santorum said.
"The reason why our campaign is winning in state after state is because people want an authentic, strong conservative leader to take on Barack Obama and not someone who just talks a good conservative game."
But Santorum's failure to win over more moderate voters and his focus on divisive culture war issues like abortion and birth control has called into question his ability to beat President Obama in the November 6 election.
"We liked Santorum for a while, but lately he has gotten too radical," Betty Harper, 76, told AFP after casting a ballot for Romney at aNew Orleanspolling station.
"Obama is out of control, I really think he is a closet Muslim," she added, echoing conspiracy theories that have dogged Obama ever since his 2008 White House runs.
Her husband, Dick Harper, said Romney is the "best man for the job" because he's a "good businessman and he won't embarrass us."
Pressure is mounting from the Republican establishment to rally behind Romney, whose 21 wins includeFlorida,OhioandMichiganall key battlegrounds in the general election.
Obama had an eight-point lead over Santorum in a hypothethical matchup that had him in a statistical tie with Romney, according to Rasmussen national survey.
But Santorum insists the only way to beat Obama is to pick a conservative candidate who can energize the party's base rather than tapping an "Obama-Lite" in the hopes of winning over moderates and independents.
And the party's conservative base isn't listening to the establishment anymore, said Steffen Schmidt, a political science professor atIowaStateUniversity.
"Since 2010 GOP incumbents and 'establishment' have been declared to be RINO's (Republican In Name Only) challenged in primaries, and generally excoriated by almost 2/3 of the Republicans voting or going to caucuses," Schmidt told AFP.
"Romney is a nice man, but I prefer Santorum because I felt he is better than the rest, morally for one thing," Dianne Cannelle, 79, said after casting a ballot inNew Orleans.
"You don't just have to have brains to be president; you have to have moral values as well."
Turnout has been low in the hotly contested, topsy-turvy Republican nominating race, but Romney has dismissed any concerns about an enthusiasm gap as he amasses an increasingly insurmountable lead.
Santorum has vowed to take the fight all the way to the Republican convention in August if Romney fails to win the 1,144 delegates needed to clinch the nomination.
Romney currently has an estimated 560 delegates, while Santorum has won 246, according to the website Real Clear Politics.
Gingrich, who has won two states, has 141 delegates, while Paul, who has not won a single contest, has 66 thanks to the proportional distribution of delegates in some states.
While Santorum's expected win inLouisianaought to provide him with some momentum, the race next shifts to states where Romney has the advantage.
The formerMassachusettsgovernor was ahead by 13 points in a Rasmussen survey of voters in the Midwestern state ofWisconsin, which heads to the polls on April 3 along withMarylandand theUScapitalWashington.
Santorum is expected to carry his home state ofPennsylvaniain the following contest on April 24, but the victory will be overshadowed if Romney is able to sweepNew York,Connecticut,DelawareandRhode Island, which also vote that day.