Only one lawmaker out of 67 in the Maltese parliament voted against the legislation, signaling its broad support on the island nation despite opposition from the Catholic Church.
Nationalist lawmaker Edwin Vassallo cited his Catholic faith and its incompatibility with what he called a "morally unacceptable" law.
"As a Christian politician I cannot leave my conscience outside the door" when voting, Vassallo said.
The Labor government had promised to introduce the bill as its first law after winning a second term last month. Both opposition parties supported it, ensuring its passage.
Prime Minister Joseph Muscat hailed the "historic" vote, saying it showed Maltese society had reached "an unprecedented level of maturity."
"We live in a society where we can all say 'we are equal,'" Muscat said as a celebration erupted outside his office in Valletta, the capital.
Indeed, the law's passage marked the latest evidence of the transformation of the once-conservative nation of about 440,000 people, where divorce was illegal until 2011.
While abortion remains banned in Malta, adoption by same-sex couples has been legal since civil unions were introduced in 2014. Last year, the number of exclusively civil marriages eclipsed the number of church weddings for the first time.
Archbishop Charles Scicluna had opposed the same-sex marriage law, reflecting the church's longstanding view that marriage can only be between a man and woman.
"I can decide that a carob and an orange should no longer be called by their name," he said in a homily a few days after parliament started debating the legislation. "But a carob remains a carob and an orange remains an orange. And marriage, whatever the law says, remains an eternal union exclusive to a man and a woman."
The aim of the law, piloted by Malta Equality Minister Helena Dalli, was to "modernize the institution of marriage" to extend it to all consenting adult couples.
Muscat had said it would be "discriminatory" to have separate laws for mixed and same-sex couples. So the amendments to existing laws included eliminating any reference to "husband and wife." In its place is now the gender-neutral term "spouse" to cover all situations.
The law also calls for the removal of the terms "father" and "mother," to be substituted by "parents." Lesbian couples who have children via medical interventions are distinguished by the terms "the person who gave birth" and "the other parent."
Other changes concern heterosexual marriages: Any reference to "maiden name" is replaced with "surname at birth," while both spouses can choose what surname to take after marriage.
The coordinator of the Malta Gay Rights Movement, Gabi Calleja, said achieving equality in marriage met the LGBT community's aspirations. Most same-sex couples consider marriage to be "the institution that best expresses the commitment and love they have for each other," Calleja said.
More than a dozen European countries have legalized same-sex marriage, all in the western part of the continent. Almost a dozen others, including Italy, have some sort of same-sex unions or civil partnerships, according to the Pew Research Center.