A small group of relatives and friends met at the farmhouse in Dunganstown, Co Wexford, to pay their respects and celebrate the late president's legacy 50 years on.
Pat Kennedy, 72, the last of the cousins to carry the famous name, said the commemoration evoked strong memories of the notorious day his third cousin was assassinated in Dallas, Texas.
The retired farmer was among relations who welcomed the president to the humble homestead where the Kennedy story began just five months before his death in 1963.
A number of events were held in and around New Ross, Co Wexford, to mark the anniversary, which is being remembered around the world.
An official State ceremony was held at the nearby JFK Arboretum, which was opened in 1968 by then Irish president Eamon de Valera.
Soldiers from the 3rd Infantry Battalion from Stephen's Barracks in Kilkenny formed a guard of honour as government ministers Brendan Howlin and Paul Keogh arrived to lay a ceremonial wreath after a lone piper played She Moved Through the Fair.
Both the Irish Tricolour and the US flag were hoisted from half to full mast, as the national anthems of both countries were sounded.
Recalling JFK's visit to Ireland, Mr Howlin said it was a watershed in Irish history.
"It instilled a renewed sense of national pride, of optimism for the future in a rapidly changing world and a belief that Ireland had a significant role to play in that world," he said.
In Dublin, Tanaiste and Foreign Affairs minister Eamon Gilmore led tributes at a wreath-laying ceremony at the US Embassy.
Mr Gilmore said Mr Kennedy's assassination was etched indelibly in his own memory and that of his generation.
"It is particularly sad for us as Irish people, given the special place which president Kennedy held in our hearts," he said.
"Just a few short months prior to his untimely death, we had rejoiced together with him and his family during his memorable visit to these shores in June 1963.
"It was a visit that brought Ireland and the United States together in a rare and moving way."
Patrick Grennan still lives at the ancestral Kennedy homestead in Dunganstown and his grandmother Mary Ryan - a third cousin of the president - was gifted his rosary beads and commander in chief dog tags after his death.
"I think it is amazing that 50 years on there's still such attention on president Kennedy," he added.
"Every newspaper we've opened in the last couple of weeks, every television station, is running something on Kennedy.
"There's a film coming out - it's just amazing how 50 years on his memory continues to capture the world.