On a June day in 1966, Kennedy, though shunned by South Africa's white government, appeared before students to decry the "racial inequality of apartheid".
That would have been provocative enough, but he also implored them to rise up and challenge the moral bankruptcy of their leaders, to be the change they wished to see.
"It is from numberless diverse acts of courage and belief that human history is shaped," Kennedy said, employing the unmistakable long vowels of his Boston accent and the trademark staccato delivery he shared with his brothers.
"Each time a man stands up for an ideal, or acts to improve the lot of others, or strikes out against injustice, he sends forth a tiny ripple of hope," said the senator, then a US presidential candidate.
"And crossing each other from a million different centres of energy and daring those ripples build a current which can sweep down the mightiest walls of oppression and resistance."
His words were a direct assault on the brutal divisions that cut across South Africa's schools, buses, beaches and suburbs.
An assault on the humiliating identification passes that the black majority were forced to carry in their own land.
And it could not have come at a more sensitive time.
It was just a few years after Nelson Mandela was first sent to Robben Island, which lies a short distance across the shimmering waters of Table Bay.
The impact of the speech was electrifying.
A local liberal newspaper, the Rand Daily Mail, hailed Kennedy's visit as the "best thing" to happen to South Africa in years.
"It is as if a window has been flung open and a gust of fresh air has swept into a room in which the atmosphere had become stale and foetid. Suddenly it is possible to breathe again without feeling choked," the paper said.
The Washington Post noted the South African government's "glacial snub".
"In the eye of the government in Pretoria, the visit is as welcome as a mild plague," the paper wrote.
An "ominous silence" followed his departure with everyone "waiting for the government's backlash", the London Observer News Service said.
One deputy minister however did take vocal umbrage, according to press clippings on the website for the 2009 film RFK In the Land of Apartheid.
"This little snip thinks he can tell us what to do," he thundered.
"He has only been in the country for three days and already he has the audacity to tell us what the remedy to our problems would be."
But still Kennedy's comments rippled across history, although it was almost three decades before apartheid ended.
Exactly two years after his speech he would die after being shot dead in a Los Angeles hotel kitchen by a Palestinian gunman.
By his graveside in Arlington National Cemetery near Washington is a quotation from what become known as his "ripple of hope" speech.
Because Kennedy also spoke soberly of America's own challenges, the venue is likely to carry extra symbolism for America's first black president. – Sapa-AFP