The 23-year-old had arrived in Singapore on Thursday after undergoing three operations in a Delhi hospital.
The attack earlier this month triggered violent public protests in India that left one police officer dead.
As news of the student’s death spread across social media in India, police sealed off large parts of central Delhi and appealed for calm.
The centre of Delhi resembled a fortress, with armed police and riot troops maintaining a heavy presence.
Indian Prime Minister Manmohan Singh said he was “very saddened” and promised to channel “emotions and energies” into a course of action.
Six men have been arrested and two police officers have been suspended following the 16 December attack.
A statement from the hospital said the woman “passed away peacefully” early on Saturday with her family by her side.
“The patient had remained in an extremely critical condition since admission to Mount Elizabeth Hospital,” hospital chief executive Kelvin Loh said.
“She had suffered from severe organ failure following serious injuries to her body and brain. She was courageous in fighting for her life for so long against the odds but the trauma to her body was too severe for her to overcome.
“We are humbled by the privilege of being tasked to care for her in her final struggle,” Kelvin Loh said.
A team of eight specialists had tried to keep the patient stable, but her condition continued to deteriorate over the two days she was at Mount Elizabeth Hospital, he added.
Officials from the Indian High Commission were also present when the patient passed away. The Indian home minister said the government had decided to send the victim overseas on the recommendation of her doctors.
Arrangements are being made to take her body back to India, said Indian high commissioner to Singapore TCA Raghavan.
In a statement issued in Delhi, Prime Minister Singh said: “It would be a true homage to her memory if we are able to channelize these emotions and energies into a constructive course of action.
“The need of the hour is a dispassionate debate and inquiry into the critical changes that are required in societal attitudes.
“Government is examining… the penal provisions that exist for such crimes and measures to enhance the safety and security of women. I hope that the entire political class and civil society will set aside narrow sectional interests… to help us all reach the end that we all desire – making India a demonstrably better and safer place for women to live in.”
The victim and her friend had been to see a film when they boarded the bus in the Munirka area of Delhi, intending to travel to Dwarka in the south-west of the city.
Police said she was raped for nearly an hour, and both she and her companion were beaten with iron bars and thrown out of the moving bus and into the street.
On arrival at the hospital in Singapore, doctors said that as well as a “prior cardiac arrest, she also had infection of her lungs and abdomen, as well as significant brain injury”.
The government has tried to halt rising public anger by announcing a series of measures intended to make Delhi safer for women.
These include more police night patrols, checks on bus drivers and their assistants, and the banning of buses with tinted windows or curtains.
The government has also said that it will post the photos, names and addresses of convicted rapists on official websites to shame them.
It has set up two committees – one looking into speeding up trials of cases involving sexual assaults on women, and the other to examine the lapses that might have led to the incident in Delhi.
But the protesters say the government’s pledge to seek life sentences for the attackers is not enough – many are calling for the death penalty.
Since the Delhi incident, several cases have been highlighted of authorities failing to respond to reported rapes.
On Wednesday, a woman committed suicide in the state of Punjab, after having tried to report to police a rape which allegedly took place last month, local media reports said.
At least one police officer involved in the case has been sacked, according to local officials.
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