Washington (CNN) -- For the first time, the U.S. Senate approved legislation that would protect gay, lesbian and transgender employees from discrimination in the workplace.
The Employment Nondiscrimination Act, or ENDA, passed the Democratic-led chamber on Thursday, 64 to 32.
Ten Republicans joined 52 Democrats and two Independents in supporting the bill. Four Senators did not vote.
Arizona Sens. John McCain and Jeff Flake became the latest GOP members to support the measure. They joined Sens. Dean Heller of Nevada, Orrin Hatch of Utah, Kelly Ayotte of New Hampshire, Lisa Murkowski of Alaska, Rob Portman of Ohio, Susan Collins of Maine, Pat Toomey of Pennsylvania, and the bill's co-sponsor, Mark Kirk of Illinois.
"The workplace is simply no place for discrimination," Collins said before the vote.
Opposition in the Republican-controlled House is strong, minimizing any chance the measure will become law. House Speaker John Boehner also opposes it.
Still, President Barack Obama urged the House to take the bill up and said he would sign it.
"One party in one house of Congress should not stand in the way of millions of Americans who want to go to work each day and simply be judged by the job they do," the President said in a statement. "Now is the time to end this kind of discrimination in the workplace, not enable it. I urge the House Republican leadership to bring this bill to the floor for a vote and send it to my desk so I can sign it into law."
The bill would provide the same protections for LGBT workers as are already guaranteed on the basis of race, gender and religion.
It would not be lawful for employers to discriminate based on a person's "actual or perceived" sexual orientation or gender identity.
ENDA's path began in earnest in 1994, the first time it was introduced in Congress.
Two years later, a version that only protected sexual orientation - and not gender identity - nearly passed the Senate but failed by one vote.
The issue was not brought up again for a vote until 2007 when the House passed the narrower version.
In 2009, an ailing Sen. Ted Kennedy, D-Massachusetts, wanted to make sure the issue didn't fall by the wayside. Just months before he died, Kennedy asked newly elected Sen. Jeff Merkley, D-Oregon, to take the reins.
Eventually, Merkley approached Kirk to help him get the measure passed.
Kirk voted for it while in the House and has been a co-sponsor. The two lawmakers lobbied colleagues, leading to Thursday's Senate vote.
Merkley remembered Kennedy's passion for the legislation, quoting him before final Senate action: "The promise of America will never be fulfilled as long as justice is denied to even one among us."
But the measure's path could end in the Senate this year as the Republican-led House appears unlikely to take it up.
"The Speaker believes this legislation will increase frivolous litigation and cost American jobs, especially small business jobs," Boehner's spokesman, Michael Steel, said.
Chad Griffin, president of the LGBT activist group Human Rights Campaign, had harsh words for Boehner.
"The Speaker, of all people, should certainly know what it's like to go to work every day afraid of being fired. Instead of letting the far right trample him again, it's time for Speaker Boehner to stand with the majority of everyday Republican voters and support ENDA," Griffin said earlier this week.
Regardless proponents are applauding Senate action.
"Equality means equality in the workplace, as much as anywhere else in our lives," said Lisa A. Linsky, trial partner and partner-in-charge of LGBT Diversity and Inclusion at international law firm McDermott Will & Emery LLP.
Opponents say ENDA will have "a chilling effect on free speech as well as religious liberty" by requiring secular businesses who have a moral objection to LGBT people to not discriminate against them.
Efforts to expand the religious protection component of the bill to secular businesses failed.
The Traditional Values Coalition says passage of ENDA would "hurt kids."
"Young students in some states are already being confused by transgender teachers," a fact sheet by the Traditional Values Coalition read. "If ENDA passes, students and children in daycare centers all across the nation will be subjected to individuals experimenting with their gender identities."
Twenty-one states currently have laws protecting lesbian and gay workers from discrimination and 17 states protect transgender workers, according to the Human Rights Campaign.
CNN's Ted Barrett and Deirdre Walsh contributed to this report