With 70 percent of precincts reporting, Romney had 42 percent of the vote, followed by Santorum with 37 percent.
Romney also picked up another victory in Arizona's winner-takes-all primary, taking all 29 of the delegates there.
Santorum quickly shot up in the polls after winning the caucuses in Minnesota and Colorado and a nonbinding Missouri primary. With his new frontrunner status, he had focused his resources on Michigan in hopes of winning an upset victory against Romney.
Romney sought to temper expectations as he lashed out at Santorum's "dirty tricks" in Michigan's open primary, but expressed confidence that voters would favor his economic plans over Santorum's "incendiary" focus on divisive social issues.
"The hardest thing about predicting what's going to happen today is whether Senator Santorum's effort to call Democratic households and tell them to come out and vote against Mitt Romney is going to be successful or not," Romney said in a morning press conference.
Santorum defended the move as standard electoral politics, saying he was targeting conservative Democrats to show he would have broad appeal in a match-up against President Barack Obama.
Democrats have also been urging supporters to head to the polls in order to prolong the negative, gaffe-ridden slug-fest which is providing ample fodder for Obama ahead of the November 6 general election.
"I think Republicans have to recognize there's a real effort to kidnap our primary process," Romney told reporters.
A pugnacious Obama waded into the race Tuesday, tearing into his Republican opponents for their vehement opposition to his efforts to save the Michigan-based auto industry.
In a barnstorming speech to auto workers gathered in the US capital, Obama accused Romney and his fellow Republicans of being on the wrong side of history and of flagrant pandering to conservative voters.
Romney has frequently accused Obama of engineering the bailout of General Motors and Chrysler to help his union supporters, but Obama said Romney's charges of crony capitalism is a "a load of you-know-what."
"They're still talking about you as if you're some greedy special interest that needs to be beaten," Obama said without naming names.
"To borrow a line from our old friend Ted Kennedy: what is it about working men and women they find so offensive?"
The Republican opposition to the bailout and focus on divisive social issues "has probably cost them Michigan in the general election," said Michael Traugott, a political expert at the University of Michigan.
"We don't have many auto workers left, but it's symbolic for general attitudes about workers in the state of Michigan," he told AFP.
The attack on unions could also undermine Republicans in rust belt states like Ohio and Pennsylvania which are key battlegrounds in the general election, especially if Obama succeeds in framing Republicans as a party of social extremists who sell out working people while pushing huge tax cuts for the rich.
Tuesday's votes come at a pivotal phase in the state-by-state nominating process that will decide which of the four remaining Republican contenders will face off against Obama.
Santorum is hoping for a major upset that will prove his surprise wins in Minnesota, Colorado and Missouri on February 7 were no fluke and could cement his position as a genuine alternative to Romney.
A staunch Christian conservative who strongly opposes abortion and gay marriage, Santorum advanced in the polls by painting himself as the authentic conservative and his multimillionaire opponent as out of touch.
But Romney put in a strong debate performance when it mattered on Thursday and has used his financial muscle to successfully portray Santorum, a former Pennsylvania senator, as a Washington insider.
If Santorum clinches Michigan, he could claim the momentum going into "Super Tuesday" -- when 10 states vote on March 6.
All four candidates have vowed to stay in the race until the party convention at the end of August, when a result might have to be brokered behind the scenes if no one reaches the magic number of 1,144 delegates.
Romney leads in pledged delegates, having won the more important states so far.
The other two candidates, former House Speaker Newt Gingrich and small-government champion Ron Paul, trail significantly in national polls.
With AFP.
