The actress - who played Lois Lane in 1978 hit Superman - died peacefully overnight at her home in Montana.
She was still working until her death on Sunday night, most recently starring in a run of The Vagina Monologues on Broadway.
The star - who was married three times - battled bipolar disorder and spent time living on the streets in 1996.
The ordeal led to her becoming a mental health advocate.
She starred alongside Christopher Reeve in the first Superman film, as well as three sequels.
She went on to gain more exposure by taking the lead role in The Amityville Horror in 1979.
She started her career as a TV actress in the 1960s, before going on to make her big-screen break opposite Gene Wilder in Quackser Fortune Has a Cousin in the Bronx.
She starred with Christopher Reeve who played Superman in the three sequels.
Reeve died in 2004 after being paralysed and wheelchair bound following a horse riding accident in 1995.