The legislation, which requires 20 percent local hiring for city-funded construction projects in the first year, increasing by 5 percentage points each year to 50 percent in the seventh year, will now become law in 60 days.
The board approved the measure by a veto-proof majority of 8-3 on Dec. 14.
The measure has drawn ire from some contractors and building trade unions as well as from the San Mateo County Board of Supervisors and other Peninsula officials, including state Assemblyman Jerry Hill, D-San Mateo.
Newsom said he has concerns about the measure, which he returned to the board unsigned.
"Local-hire policy is a complex arena that requires a delicate balance," the mayor wrote in a letter to the board on Thursday.
Newsom said San Francisco should work with nearby jurisdictions to make sure the ordinance is applied intelligently.
"There is much outreach to be done with our neighboring cities and counties who have expressed significant concern with the impact of this legislation on their local workforces," Newsom said.
Newsom said the city also needs to work closely with the business community.
"To speak plainly, the Board of Supervisors can pass any number of local hiring policies, but without a strong working relationship between the construction departments, the Office of Economic and Workforce Development and the trades, these efforts will be frustrated by implementation challenges and delays," he said.
Supervisor John Avalos, who sponsored the legislation, has called it "a new deal" for San Francisco that would bring more jobs to the city's economically depressed neighborhoods.
Avalos has called the ordinance "the nation's strongest local hiring mandate."
Assemblyman Hill on Friday called the ordinance "regrettable" and said he has asked the state Legislative Counsel's office to look into potential legal action to limit the impact on construction projects involving state dollars.
Hill said he thinks the ordinance is unfair to San Mateo County residents who work on projects in San Francisco and could "lead to wars" between Bay Area counties over restrictions for hiring people for local projects.
Hill said he also believes the ordinance is harmful to the region's economy at a time when there is a high unemployment rate.