A new ordinance will affect many of the roughly 10,000 U.S. companies that contract with the city to provide everything from banking services to office supplies.
Critics call the policy ill-conceived and costly, approved without ample study or public notice.
"We don't think it's good public policy for the city to tie its hands in the way this ordinance mandates," said Dennis Wyss, a spokesman for Bank of America, the nation's third-largest bank.
"We think San Francisco taxpayers get the highest-quality services for their money when the city keeps its options open."
Supporters say it's a basic anti-discrimination measure aimed at granting all unmarried domestic partners - although most of them in San Francisco are same-sex couples - the same rights enjoyed by wedded couples.
Joe Leslie, a 52-year-old assistant vice president at Bank of America, with his partner Michael, will benefit from the policy.
Leslie said he and Michael are "as loving as any married couple that ever walked this Earth," and for co-workers' spouses to receive better benefits is simply unfair.
"We do the same work, our spousal status is virtually the same. (Yet) they get benefits I don't get," Leslie said.
The Gap Inc., Levi Strauss & Co. and the Walt Disney Co. have started domestic partner policies. In San Francisco, Bank of America officials have discussed such a policy but haven't enacted it.
"If it's good enough for Mickey Mouse, it's good enough for San Francisco," said city Supervisor Tom Ammiano, the measure's co-author.
The city's Board of Supervisors gave the ordinance unanimous approval after considering it since last February. Mayor Willie Brown signed it in early November. Brown and Ammiano said it is the first such ordinance in the nation.
But there is no official effective date for the measure; city officials say they expect it to go into effect in six months, but they are still working on the details
That leaves companies without a clear idea of how they'll cope.
"We really feel the supervisors did not do their homework," said Carol Piasente, a spokeswoman for the city's 1,950-member Chamber of Commerce. "They're not prepared to answer all the questions that come up because they didn't think of all the details."
Businesses wonder who, precisely, is affected. Does the legislation apply, for example, to hundreds of airlines that technically do business with the city every time they pay a gate tax at San Francisco International Airport? Or to nonprofit agencies that provide services for the homeless? Most importantly, how much will it cost?
"We don't have a clue about the costs. That's the problem. Nobody knows," Piasente said.
"When you do this kind of legislation at a local level, you're imposing costs on local companies that make them not competitive in the bigger marketplace," Piasente said. "It's the kind of thing that, if done on a national level, some of the unfairness issues would be taken away."