North Carolina voters made their state the 32nd in the nation to recognize marriage as a union of only one man and one woman.
With 50 out of 100 counties reporting, the constitutional amendment was winning, 61 percent to 39 percent.
The measure bans same-sex marriage.
Evan Wolfson, leader of Freedom to Marry, said the amendment is "a last gasp of discrimination" against gay marriage.
But supporters were jubilant. "And North Carolina is for marriage," Vote for Marriage North Carolina tweeted shortly after 9 p.m.
In other North Carolina primary races, Democrat gubernatorial candidate Walter Dalton was headed to a win over Bob Etheridge, while Republican candidate Pat McCrory coasted to an easy win over other contenders.
The presidential primaries were done deals, with President Obama and Mitt Romney winning their respective contests handily.
Before Tuesday's vote, the gay marriage issue received national attention: Vice President Joseph R. Biden said Sunday he is "absolutely comfortable" with gay marriage, while Education Secretary Arne Duncan said he supports gay marriage.
Former President Bill Clinton recorded phone messages urging voters to reject the amendment, and North Carolina Gov. Beverly Perdue, who is not seeking re-election, urged voters to reject the amendment.
"Whatever your personal, moral or religious views may be, writing discrimination into North Carolina's constitution is just plain wrong," the Democratic governor said, saying the amendment poses a threat to the health and well-being of unmarried couples, families and businesses.
But supporters were backed by countless clergy, including renown evangelist Billy Graham, who took a rare political stance and called for a "yes" vote among the faithful.
In early voting, more than 507,000 people cast ballots, more than in 2008 when President Obama was a presidential candidate, according to the Carolina Transparency Project, conducted by Civitas Institute.
Unaffiliated voters mostly took Republican ballots, potentially indicating a vote for the amendment.
Joe Easterling, who described himself as a devout Christian, voted for the amendment.
"I know that some people may argue that the Bible may not necessarily be applicable, or it should not be applicable, on such policy matters," he said. "But even looking at nature itself, procreation is impossible without a man and a woman. And because of those things, I think it is important that the state of North Carolina's laws are compatible with the laws of nature but, more importantly, with the laws of God."
Linda Toanone, who said she voted against the amendment, said people are born gay and it is not their choice.
"We think everybody should have the same rights as everyone else. If you're gay, lesbian, straight whatever," she said.
Later this year, voters in Minnesota, Maine and probably Washington state and Maryland will have gay-marriage measures to vote on.
Like many states with constitutional marriage amendments, the North Carolina amendment disallows other types of domestic unions from carrying legal status.
Amendment supporters said that this would not prevent companies and individuals from establishing contracts regarding benefits and protections.
But opponents warned that the amendment would upend established arrangements and harm unmarried couples and their families.
• This article is based in part on wire service reports.
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