Current federal law prohibits discrimination on the basis of sex, race and national origin. But it doesn't stop an employer from firing or refusing to hire workers solely because they are gay, lesbian, bisexual or transgender.
The bill would bar employers with 15 or more workers from using a person's sexual orientation or gender identity as the basis for making employment decisions, including hiring, firing, compensation or promotion.
The Senate vote would come five months after Supreme Court rulings affirming gay marriage and granting federal benefits to legally married same-sex couples. It would be the first major piece of gay rights legislation since Congress repealed the ban on gays serving openly in the military in December 2010.
Collins said the military's relatively smooth implementation of that law despite dire warnings have made Americans more receptive to the nondiscrimination law.
"People intuitively think that it is unfair to discriminate against someone based on their sexual orientation," said Collins, who led the fight on gays in the military. "Just as it would be unfair to refuse to hire or fire them based on religion or race or gender. In fact, when I talk to constituents, they're surprised that it's still legal under federal law."
The measure faces strong opposition from established conservative groups such as the Family Research Council. That group says the bill carves out special protections for sexual orientation, would lead to expensive lawsuits against employers, and could undercut the ability of employers to establish reasonable standards for dress and grooming.
Heritage Action said Friday that the bill would "severely undermine civil liberties ... and trample on religious liberty" while potentially undermining job creation. The conservative organization called for a vote against the bill and said it would record the vote on its legislative scorecard.
It is unclear whether Republican leaders in the House will even bring the bill up for a vote after the Senate acts.