Media reports said a round of applause went up in court as the judgement was read out on Friday.
The Supreme Court said the 23-year-old woman had suffered a "devastating hour of darkness" as it rejected an appeal against the death penalty, which was handed down in 2013.
"If at all a case warrants the death sentence it is this case," said Judge R Bhanumati.
Jyoti Singh, a 23-year-old physiotherapy student, was raped and left for dead by a gang of five men and a teenager after she boarded a private bus while going home from the cinema with a male friend.
She died of grievous internal injuries 13 days later.
The brutality of the attack, and her determination to survive long enough to identify her attackers to police, triggered large-scale street protests in Delhi.
Four men were convicted in September 2013 for murder, gang rape, theft, conspiracy and "unnatural acts" after a seven-month trial in a fast-track court.
A fifth man, the suspected ringleader, was found dead in jail in a suspected suicide, while the 17-year-old was sentenced to three years in a detention centre and has since been released.
Sentencing the four in 2013, Judge Yogesh Khanna said the case fell into the "rarest of rare category" which justifies capital punishment in India.
But defence lawyer A P Singh called the sentence "unjust" and said he would file a review petition -- the next stage in the appeals process -- after examining the ruling.
"We are sure the court will change its decision once we appeal and justice will be delivered to the poor," he said outside the court.
Media reports said a round of applause went up in court as the judgement was read out on Friday at the end of an appeal hearing that began last year.
Women's rights activist Ranjana Kumari called it a "historic judgement".
"This is a historic message to all the people, the criminal mindset who wrong women, who inflict violence on women, to know that if you do something like this you will be also paying for it by the severest punishment that exists in our laws of the land," she said on Indian news channel NDTV.
The accused, low-paid migrants to New Delhi, brutally assaulted Singh behind tinted windows for 45 minutes, penetrating her with an iron bar.
Her injuries were so severe that she died nearly a fortnight later in a Singapore hospital. She had only briefly regained consciousness, telling family and friends of her desire to see her attackers burn to death.
The case led to mass protests in Delhi and prompted the government to amend the law to introduce tougher punishments for rapists, including the death penalty for repeat offenders.
Nonetheless, levels of sexual assault remain extremely high in the Indian capital, which registered 2,199 rape cases in 2015 -- an average of six a day.
Activists say the true number is likely much higher, with many attacks going unreported because of the social stigma attached to sexual crimes.