The house was home to the "Some Like It Hot" screen siren for the final six months of her life up to her death from a drug overdose in 1962.
More than half a century on, Monroe remains one of the most beloved figures in US pop culture, and fans as well as conservationists have closely followed a row over the future of the home.
Property heiress Brinah Milstein and her reality TV producer husband Roy Bank bought the Spanish Colonial-style home in the swanky Brentwood neighbourhood last summer for $8.35 million.
The couple owned the house next door and intended to combine the two properties. That construction would have involved razing the Monroe home.
But when a demolition permit was issued last September, a furore quickly followed, and local politicians moved quickly to designate the building protected status.
Last month, the owners sued the city of Los Angeles for "illegal and unconstitutional conduct."
Their petition noted Monroe had "occasionally" lived in the home for "a mere six months", and the couple claim that more than a dozen previous owners since 1962 have already changed the building beyond recognition.
Those objections were overruled Wednesday, as city councillors approved the designation of the house as a historic cultural monument.
Monroe bought the 3,000-square-foot single-story hacienda in 1962 just after her divorce from playwright Arthur Miller.
"There is no other person or place in the city of Los Angeles as iconic as Marilyn Monroe and her Brentwood home," said councillor Traci Park, whose district includes the house in question.
"Some of the most world-famous images ever taken of her were in that home, on those grounds and near her pool.
"There is likely no woman in history or culture who captures the imagination of the public the way Marilyn Monroe did. Even all these years later, her story still resonates and inspires many of us today."
Monroe's smouldering looks and breathy delivery made her one of the most bankable movie stars of her era.
The "Gentlemen Prefer Blondes" star was linked during her lifetime with some of the most eligible men of her era, including president John F. Kennedy, famously singing "Happy Birthday, Mr President" at Madison Square Garden.
