In addition, Democrat Elizabeth Warren, a Harvard law professor, unseated Republican Sen. Scott Brown, giving Democrats a second pickup of the night of a Republican Senate seat.
The other seat was Democratic Rep. Joe Donnelly's victory in Indiana against Republican Tea Party favorite Richard Mourdock.
Obama tallied 61 percent of the vote to Republican presidential nominee Romney's 38 percent, with virtually all votes counted.
Libertarian Party nominee Gary Johnson collected 1 percent of the vote and Green Party nominee Jill Stein, a Massachusetts physician, got 0.6 percent.
Warren won 54 percent to Brown's 46 percent, with almost all votes counted. Brown conceded late Tuesday night.
Romney was governor of Massachusetts from 2003 to 2007. As governor, he helped develop and enact into law the Massachusetts healthcare reform legislation -- the first of its kind in the nation -- that provided near-universal health insurance access through state-level subsidies and individual mandates to purchase insurance.
He also presided over the elimination of a projected $1.2 billion to $1.5 billion deficit through a combination of spending cuts, increased fees and the closure of corporate tax loopholes.
Romney did not seek re-election in 2006, focusing instead on his campaign for the Republican presidential nomination in 2008.
In a key House race, Rep. John F. Tierney held on to win a ninth term in northeastern Massachusetts' 6th Congressional District. He edged past Republican Richard Tisei 48 percent to 47 percent, with the victory margin of just 3,650 votes out of 355,556 votes cast.
Libertarian Party nominee Daniel Fishman won 4.5 percent.
Politico ranked the House race as one of the country's 10 nastiest.