Enacted 15 years ago, the law -- known by its acronym DOMA -- effectively denies federal benefits to gays and lesbians who now can legally marry in six states and the District of Columbia.
Its repeal, sponsored by Diane Feinstein, a Democrat from California and former mayor of gay-friendly San Francisco, would be a victory for the gay rights movement -- and a major setback for social conservatives.
"We have 131,000 married (gay) couples, and the discriminatory nature of DOMA is showing up throughout the business and professional communities of this country," said Feinstein in a pre-vote debate.
Under DOMA, marriage is defined in federal law exclusively as "a legal union between one man and one woman as husband and wife." It also enables states without gay marriage the power to not recognize same-sex vows made elsewhere.