He died of natural causes at 8.13 p.m. on Sunday at a hospital in Kern County, the California Department of Corrections and Rehabilitation said in a news release.
The news of his death was confirmed by Debra Tate, the sister of his most famous victim, actress Sharon Tate, who was heavily pregnant with film director Roman Polanski's baby when she was stabbed to death by his followers.
"This could be the end of an era or just the beginning," she declared, adding: "I said a prayer for his soul."
Prison officials said it's "undetermined" what will happen to Manson's corpse as he has no next of kin, the US media reported.
The diminutive and charismatic Manson orchestrated a wave of violence in August 1969 that took the lives of seven people, spawned headlines worldwide and landed him and his "Manson Family" of followers in prison for most of the remainder of their lives.
Manson served nine life terms in California prisons and was denied parole 12 times. His notoriety made him a cult figure to those fascinated by his dark apocalyptic visions. With a Swastika tattooed on his forehead, Manson was the very embodiment of evil.
The brutal killings began on August 9, 1969, at the home of Tate and Polanski, while he was out of the country at the time. The first set of victims were Tate; a celebrity hairstylist named Jay Sebring; coffee fortune heiress Abigail Folger; writer Wojciech Frykowski; and Steven Parent, a friend of the family's caretaker.
The next evening, another set of murders took place. Supermarket executive Leno LaBianca and his wife, Rosemary, were killed at their home. Over the course of two nights, the killers took the lives of seven people, inflicting 169 stab wounds and seven .22-caliber gunshot wounds.
The killings collectively were known as the Tate-LaBianca murders. Manson was not at the scene of either slayings, but was nonetheless convicted of murder for directing his followers.
He was sentenced to death in 1971. But before the death sentence could be carried out, California outlawed capital punishment and his sentence was reduced to life.
His "Manson Family" was made up mostly of disaffected young women, some of whom became killers under his tutelage. It occupied a dark, persistent place in American culture and American commerce.
It inspired, among other things, pop songs, an opera, films, a host of internet fan sites, T-shirts, children's wear and half the stage name of the rock musician Marilyn Manson.
Gathering young followers around him in the late 1960s, Manson claimed to believe in a coming race war in America. He planned to hasten the war and emerge as the leader of a new social order -- a vision he nicknamed "Helter Skelter", after a Beatles song Manson became obsessed with.
Prosecutors argued that Manson hoped African-Americans would be blamed for the Tate-LaBianca killings, heightening racial tensions.
Manson convinced a number of his followers that he was the reincarnation of Jesus Christ.
He was born on November 12, 1934, in Cincinnati, to an unmarried 16-year-old girl who supported herself on petty crime. Mason never knew his father and ended up in a series of foster homes and reformatories.
He was married twice but both marriages ended in divorce. Manson spent most of his teens and 20s in and out of prison for crimes that started with robbing liquor and grocery stores before he stole cars, pimped women, and committed forgery. He ended up orchestrating cold-blooded murders.
In prison, Manson became obsessed with music and learned to play the steel guitar. He attempted to ingratiate himself with the Hollywood glitterati, using his guitar and songwriting as a wedge. He managed to get one song on the Beach Boys' album "20/20" in 1968. It was titled "Cease to Exist" but revised and retitled "Never Learn Not to Love".
Mason reportedly leaves three sons and was recently engaged to 29-year-old Afton "Star" Burton until she called off the wedding.