Gays and lesbians can be ordained as ministers and lay leaders after a vote by the US Presbyterian Church, which thus became the fourth mainline Protestant church to do so.
The decisive vote capping a three-decades-long debate was cast by a regional group in Minnesota, the Los Angeles Times reported.
With the decision, the Presbyterian Church joins the Episcopal and Evangelical Lutheran Churches as well as the United Church of Christ in allowing homosexuals to openly serve as ministers and lay leaders.
The measure will however allow regional organizations to decide the issue for themselves.
"This is an important moment in the Christian communion," Michael Adee, a Presbyterian elder who heads an organization that fought for gay ordination, was quoted as saying by the LA Times.
"I rejoice that Presbyterians are focusing on what matters most -- faith and character, not a person's marital status or sexual orientation."
The change to the Presbyterian Church constitution was approved last summer by the church's General Assembly, its governing body.
But under church rules, such changes must then be ratified by a majority of the 173 regional organizations known as presbyteries.
Late Tuesday, at a meeting in a Minneapolis, Minnesota suburb, the Twin Cities Presbytery became the 87th regional body to vote yes, the LA Times said.
The vote reflects changing attitudes in recent years, as more Americans have come to support the integration of homosexuals into institutions that long banned them, such as the military.
Linda Fleming, an elder and deacon at Knox Presbyterian Church in Ladera Heights, California, said she was among those who had changed their minds.
"I finally decided at the age of 63 that it is inevitable," she said, according to the LA Times. "I think it's like letting black people come to white churches, or letting women become ministers."
She still expressed surprise at the vote.
"For the Presbyterian Church, which is a mainline church, a graying church, it's something."
The US Congress voted late last year to lift a ban on homosexuals serving openly in the military, reversing the "Don't Ask, Don't Tell" compromise of 1993 that required gay soldiers to keep quiet about their sexual orientation.