The million-strong United Church of Christ (UCC) has become the first major US Christian denomination to come out in support of gay marriage.
Massachusetts is currently the only state to allow same-sex marriages
The UCC's general synod passed a resolution affirming "equal rights for couples regardless of gender".
The decision is not binding and will not require pastors to marry same-sex couples, though some already do.
Several other Churches have endorsed gay civil partnerships but have not given them the status of marriage.
The Episcopal Church (the US branch of the Anglican Communion) and the Evangelical Lutheran Church permit same-sex unions, while the Presbyterian Church is seeking to resolve severe disagreements over the issue.
US conservatives are seeking to amend the country's constitution to ban same-sex marriage, which is currently legal only in the state of Massachusetts.
Vermont allows same-sex civil unions, giving gay couples the same benefits as married couples on matters such as life insurance, health care and child custody.
Neighbouring Canada's lower house of parliament passed a law allowing gay marriages last week, which is expected to come into force in July.
Around 80% of the UCC's 884-member synod voted in favour of the resolution on Monday.
Rev John Thomas, the UCC president and general minister, noted the significance of passing the resolution on US Independence Day.
"On this July 4, the United Church of Christ has courageously acted to declare freedom, affirming marriage equality, affirming the civil rights of gay... couples to have their relationships recognised as marriages by the state, and encouraging our local churches celebrate those marriages," he said at a news conference after the vote.
UCC churches are autonomous, and the synod cannot dictate policy to individual congregations.
Nevertheless, opponents of the resolution said it could cause a split.
"I would like to see us stay in the denomination and network for positive change, said Rev Brett Brecker, who represents a conservative group in the Church.
"However, many of my members have expressed very clearly that this decision would cause great consternation and that, if this happened, they would want to see us leave."
The UCC, which is strong in New England, an area traditionally more tolerant of same-sex unions than other parts of the country, became the first major denomination to ordain an openly gay minister in the early 1970s.
It declared itself to be "open and affirming" of gays and lesbians 20 years ago.
The Church has almost 6,000 congregations and 1.3 million members.