The Democratic-led Senate has confirmed all of Obama's second-term Cabinet nominees to come to a vote.
Perez's confirmation comes at a politically sensitive moment for Republicans, who have been eager to court Hispanic voters after most flocked to Democrats in the 2012 election. Latino groups have strongly backed Perez to lead the Labor Department.
Perez is not new to confirmation battles. GOP lawmakers delayed a confirmation vote for his current position at the Justice Department for more than six months in 2009, raising many of the same concerns. He ultimately received a bipartisan vote of 72-22.
Perez, who in 2002 became the first Latino to win a seat on the Montgomery County Council, launched a brief run for Maryland attorney general in 2006. He was knocked off the ballot by the state Court of Appeals, which found he lacked the 10 years' legal experience in Maryland required by the state constitution.
Gov. Martin O'Malley then picked Perez to serve as the state's labor secretary, a job Perez held from 2007 until 2009.
In Maryland, Perez used the labor department to implement regulations aimed at stemming the foreclosure crisis.
He pushed to shift oversight of adult education programs to his agency, a move that led to a turf battle with state education officials. And he beefed up enforcement of the state's minimum wage law.
If confirmed, Perez would take over the Labor Department at an important time. The department will be a key player in the administration's plan to overhaul the nation's immigration laws, an effort that has gained momentum on Capitol Hill. Obama has also proposed raising the minimum wage.
The Harvard-educated native of Buffalo, N.Y., said he would make job creation a top priority at the department, along with enforcing wage and workplace safety laws and reauthorizing federal job training programs. He repeatedly said he would keep an open mind on controversial issues.
"We believe he is the right man for the job," said Sen. Barbara A. Mikulski, a Maryland Democrat and member of the labor committee. "Tom grew up with public service in his DNA."