Manson "died of natural causes at 8:13 pm (0213 GMT Monday) on Sunday" at a hospital in Kern County, the California Department of Corrections and Rehabilitation said in a brief statement.
Debra Tate -- the sister of Manson's most famous victim, Sharon Tate -- told celebrity website TMZ that she received a call from prison officials notifying her of Manson's death.
In the late 1960s, Manson headed an apocalyptic cult that committed random murders in upscale mostly white neighborhoods of Los Angeles -- unleashing a wave of panic in the city and beyond.
His "Family" disciples committed at least nine murders, but it was the horrific killing spree of seven people on August 9-10, 1969 that sealed his notoriety -- and earned him life in prison.
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The famous victim was 26-year-old movie actress Sharon Tate, the heavily-pregnant wife of director Roman Polanski, who pleaded for the life of her unborn child before she was stabbed to death.
Manson was not present, but ordered the killings.
One of his followers, Susan Atkins, carried out Tate's murder, after which she tasted the actress's blood and wrote "PIG" with it on the home's front door.
The sentences were later commuted to life in prison.
During his marathon trial, Manson -- with a beard, long unwashed hair, and a swastika tattooed on his forehead -- was portrayed as a drug-crazed loner with mesmerizing powers of persuasion.
Upon his death, he had been in prison in California since 1971, during which he applied for parole 12 times, telling the court on the last occasion in 2012 that he was "a very dangerous man."
In a 1981 interview conducted from jail, Manson said he had already spent most of his life in prison and felt at home there.
Manson was born on November 12, 1934 in Cincinnati in the Midwestern US state of Ohio to a 16-year-old mother, and grew up without knowing his father.
After he was repeatedly caught stealing, as a 13- year-old teen he was placed in a juvenile correctional facility and remained in detention, shifted between various facilities, until he was freed on parole in 1954.
While back in jail he learned that his wife had given birth to a son, but she asked for a divorce and left with the child.
Released again in 1958, Manson was married again a year later, to a prostitute who went by the name Candy Stevens and who would remain his wife until 1963.
By then, Manson was already back in prison for violating his parole, and would remain there until 1967 when he was released at the height of the hippie era.
At the outset a nomadic community, it later set up base in a ranch in California's Death Valley. The "Family" lived on the fringes of society and Manson had at least one child with one of his followers.
Manson became obsessed with the Beatles, and embraced a twisted philosophy inspired by lyrics of the legendary group.
Describing himself as a reincarnation of Jesus Christ, Manson arranged a series of murders in a bid to trigger a race war he dubbed "Helter Skelter," a term taken from the Beatles song of the same name.
Manson himself published a music album in 1970, re- issued as a CD in 2006.
In prison, he was granted permission in 2014 to wed then 26-year-old Afton Elaine Burton, described in US media as a slender brunette, who had been visiting him. But the 90-day license expired without the ceremony going ahead.