In an election-year milestone, the clerk's office in Cambridge was due to open its doors at midnight last night for applications from same-sex couples, while seven couples who successfully sued for the right to marry will wed in Boston.
"May 17 is a historic day. It's the day that marks a new chapter of equality for gay and lesbian families," activist Marty Rouse said. "For the first time in US history, we can receive the critical legal rights and protections that come only through marriage."
Despite a number of challenges, the state supreme court's November ruling legalising gay marriage has stood. The court gave Massachusetts legislators 180 days to work out how to ensure equality at the altar, and now the time is up.
"Whether and whom to marry, how to express sexual intimacy, and whether and how to establish a family - these are among the most basic of every individual's liberty and due process rights," the majority opinion said.
"And central to personal freedom and security is the assurance that the laws will apply equally to persons in similar situations."
Local legislators, national politicians and rightwing lobbyists have all sought in vain to reverse the court's decision or reduce its impact, while gay activists across the country have tried to capitalise on the ruling to test the boundaries in other states.
Thousands of same-sex couples were married at San Francisco City Hall earlier this year but the marriages were not recognised by the state of California. A mayor in New York state is being prosecuted after performing gay marriages in February.
The final effort to block gay marriage in Massachusetts failed on Friday, when the US Supreme Court resisted a last-minute legal challenge filed by conservative opponents of same-sex weddings.
A federal appeals court has agreed to hear the case next month, but by that time clerks will probably have granted hundreds of marriage licences to homosexual couples.
The majority of Americans are against gay marriage but in favour of civil unions for same-sex couples.
President George Bush has announced that he will support an effort to amend the constitution to define marriage as an exclusively heterosexual institution.
His Democratic challenger, John Kerry, a senator from Massachusetts, is also opposed to gay marriage.
Despite protests from the state governor, Mitt Romney, some of tomorrow's licences will be granted to out-of-state gay couples who have travelled to Massachusetts specifically to get married.
Mr Romney tried to resurrect an almost century-old law to stop such unions, saying he was afraid his state could become "the Las Vegas of same-sex marriage".
But clerks noted that the statute in question had not been applied to heterosexual couples for many years, and plan to issue licences to all gay couples from outside the state who request them. Gay rights advocates say they will challenge the law.