With all precincts reporting Wednesday, Proposition D had around 63 percent of the votes in Tuesday's election.
Two competing measures to regulate medical pot sales lost by around the same margin.
Proposition D caps the number of pot clinics in the city at 135, far below the roughly 1,000 that operated several years ago. It also increases taxes on the dispensaries and sets rules about their hours and distances from schools and parks.
The measure was backed by both mayoral candidates. Supporters portrayed it as a balanced way to deal with neighborhood concerns about loitering and crime from pot shop proliferation.
"I think the proposition just made sense to people," said Yes on Proposition D campaign spokeswoman Kerry Townsend Jacob. "It was a way to make sure that patients get the medicine and also make sure that people kept their neighborhoods safe."
"We do believe it will work well," she said.
Medical marijuana has been legal in California since voters approved it in 1996. However, regulation of so-called pot shops has been haphazard in many communities, none more so than LA. The number of dispensaries in the city surged since 2007, prompting a series of unsuccessful efforts by city lawmakers to bring order to the industry.
Those failures led to the three propositions that qualified for Tuesday's ballot.
Proposition D's major rival, Proposition F, contained no limit on the number of marijuana clinics, but it would have imposed stringent controls such as audits and background checks on employees. It was defeated by a "no" vote of around 59 percent.
Proposition E, which also contained a cap on dispensaries, received a "no" vote of more than 65 percent. Its defeat was expected after its backers threw their support to Proposition D.
California law is at odds with federal statutes, which outlaw marijuana possession and sales, even for medical purposes. Raids on dispensaries have continued under the Obama administration, disappointing medical marijuana supporters.
In LA, the outcry for oversight of pot shops intensified as the number of dispensaries grew. Residents complained that some shops were nothing more than fronts for drug dealers.
Three years ago, an ordinance was passed that slashed the number of shops from roughly 1,000 to 70. But the city was bombarded with dozens of lawsuits by dispensaries and the law expired last year, leading to another surge of pot shops.
Last summer, the city approved a ban but two months later repealed it after enough signatures were gathered to get the measures on the ballot.
Earlier this month, communities were given better guidance on the issue when the state Supreme Court ruled cities and counties can ban dispensaries.