The vote is not binding on individual churches, but could cause some churches to leave the fold.
Roughly 80 percent of the members of the church's General Synod voted to approve the resolution. They debated for about an hour before voting.
On Sunday, a committee of about 50 United Church of Christ representatives gave nearly unanimous approval to the resolution, recommending that the General Synod approve it. It was supported by the UCC's president, John H. Thomas.
Traditionally strong in New England, the liberal denomination of 1.3 million members has long been supportive of gays and lesbians.
The committee also voted against an alternative resolution defining marriage as between one man and one woman. A small group of conservative congregations had proposed that ammendment, and suggested that approval of gay marriage could lead to the church's collapse.
The church was criticized last year for its television advertising campaign featuring a gay couple, among others, being excluded from a church. CBS and NBC rejected the 30-second ads.
In the early 1970s, the UCC became the first major Christian body to ordain an openly gay minister. Twenty years ago, it declared itself to be "open and affirming" of gays and lesbians.
The same-sex resolution was submitted by the Southern California and Nevada Conference. The resolution specified that bisexual and transgender persons merit the same support and protections as gays and lesbians.
UCC churches are autonomous, meaning the General Synod does not create policy for its more than 5,700 congregations.
No hard data exist on how many gays and lesbians are in the UCC.
The Rev. Rebecca Voelkel of Cleveland, national interim director of the UCC Coalition for Lesbian, Gay, Bisexual and Transgender Concerns, said about 2,000 people are on the group's mailing list and about 1,000 clergy or seminarians are gay. The denomination has 10,323 ordained ministers.