Aruna Shanbaug, 67, died at 8.30am local time, Dr Avinash Supe, dean at the King Edward Memorial hospital in Mumbai, confirmed to CNN.
Shanbaug, who used to work as a staff nurse at the hospital, "was suffering from pneumonia for the past week and later suffered a cardiac arrest," Dr. Supe said.
"She was put on a ventilator during that time. She was being fed with a tube and had been in a vegetative state for the past 42 years," he said.
Supe referred to Shanbaug as a victim of sexual assault in 1973.
Pinki Virani, an author and journalist based in Mumbai, wrote a book entitled "Aruna's Story" in 2000, detailing Shanbaug's ordeal. In the book, Virani claimed Shanbaug was brutally sodomized and strangled with a dog chain by a sweeper at the hospital where she had worked.
On March 7, 2011, Virani submitted a petition to the supreme court of India for euthanasia
for Shanbaug, a practice which is illegal in the country. But her petition was rejected by the court.
However, as a result of Shanbaug's case, the supreme court legalized passive euthanasia in the same year,
subject to restrictions. The method is described in the court's report as "withholding or withdrawing medical treatment including discontinuance of life supporting systems."
"The greatest irony is that it was because of her (that) the euthanasia (judgment) was passed, but she never benefited from it", Virani told CNN.
"She is in peace, at last, and so am I," she said.
There has been an outpouring of grief on Twitter, as well as opinions voiced on euthanasia and praise given to the hospital.
A chief minister of a southern state in India also expressed sympathy.
But for many, Shanbaug continues to be the face of an ongoing euthanasia debate in the country.