He was born in Durban but moved to Johannesburg to work as a journalist for Drum magazine. He also worked for the Golden City Post and was the first black journalist to work at the Rand Daily Mail where he provided a black perspective for the newspaper’s predominantly white readership.
He soon realised that black writers had very few creative outlets and so founded a literary journal The Classic. Can Themba, a fellow Drum journalist, was a contributor to this. During this time he also worked closely with Nadine Gordimer.
He was awarded a Nieman Fellowship in 1964 to study journalism at Harvard College in the USA. However, the apartheid government rejected his application for a passport. As a result, he was forced to leave South Africa on an exit permit which meant that he could not return.
Nakasa soon found that racism existed in America as well, albeit more subtle. Nakasa didn't like New York and soon moved to Cambridge, Massachusetts where he spent his time at Harvard steeped in the somber business of education.
Although he learnt a lot, he was isolated and became homesick. He became depressed at being exiled and died after a fall from a high rise building in New York.
His death by suicide was an apartheid tragedy, and a tragedy of exile. He wrote articles for several newspapers after leaving Harvard, appeared in the television film The Fruit of Fear and was planning to write a biography of Miriam Makeba. But two days before his death he told a friend, I can't laugh anymore and when I can't laugh I can't write. 
A headstone placed by the Nieman Foundation 30 years later simply reads:
Nathaniel Nakasa May 12, 1937 – July 14, 1965. Journalist, Nieman Fellow, South African.
— 1038 (the tombstone number), .
The Print Media Association, the South African Nieman Alumni, and the South African National Editors' Forum subsequently established an annual award for courageous journalism, which is named after him.
The truth is that he was a new kind of man in South Africa he accepted without question and with easy dignity and natural pride his Africanness, and he took equally for granted that his identity as a man among men, a human among fellow humans, could not be legislated out of existence, even by all the apartheid laws in the statute book, or all the racial prejudice in this country. He did not calculate the population as sixteen millions or four millions, but as twenty. He belonged not between two worlds, but to both. And in him one could see the hope of one world. He has left that hope behind; there will be others to take it up.
— Nadine Gordimer , The World of Nat Nakasa
A bid was launched in May 2014 to return his body to South Africa.
- The World of Nat Nakasa : selected writings of the late Nat Nakasa / edited by Essop Patel ; with an introduction by Nadine Gordimer, Ravan Press, 1971, ISBN 0-86975-050-X
- Good-looking Corpse: World of Drum - Jazz and Gangsters, Hope and Defiance in the Townships of South Africa, Mike Nicol, Secker & Warburg, 1991, ISBN 0-436-30986-6
- "Background on Nat's Life". SA National Editors Forum. Retrieved 2007-05-11.
- "Ndazana Nathaniel Nakasa". S A history. Retrieved 2007-12-03.
- "US bid to repatriate Nakasa's remains". Times Live. 18 May 2014. Retrieved 18 May 2014.