The young leader's brutal televised death, a dark turning point event in an era gripped by the Cold War nuclear stand-off and bloodshed in the jungles of Vietnam, shocked a global audience of millions.
Five decades on the wound is still raw, with many still obsessed by the conspiracy theories surrounding his death, and others gripped by regret for the America they imagine might have been.
Across the nation, at ceremonies large and small, many took comfort in reflecting upon the words of a charismatic man whose soaring rhetoric and call to service continues to inspire.
Across the Atlantic too, Kennedy was remembered.
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A wreath laying ceremony was planned in the Berlin neighbourhood where Kennedy gave his famed Cold War-era "Ich bin ein Berliner" speech to a rapturous crowd.
At Kennedy's tomb in Arlington Cemetery outside Washington, two kilted pipers from the Black Watch of the British army, repeated a tribute their regiment had performed at the funeral 50 years ago.
In a proclamation ordering flags be lowered at government buildings and even private homes, Obama recalled Kennedy's leadership in the Cuban Missile Crisis, his speech in Berlin and his drive to advance the rights of African Americans and women.
"Let us face today's tests by beckoning the spirit he embodied -- that fearless, resilient, uniquely American character that has always driven our Nation to defy the odds, write our own destiny, and make the world anew."
The anniversary has sparked a prolonged period of national and media reflection on the unfinished tenure of the nation's 35th President, his tragedy-stricken family and the evocative period in the early 1960s when his political star illuminated the world.
He was the fourth US president to be killed in office, but the first whose death was caught on film.