Thousands of people bowed their heads or clasped hands with loved ones in Dealey Plaza yesterday to mark the precise moment of Kennedy's assassination.
The silence was broken with the singing of America the Beautiful by the US Navy choir.
The moment of reflection came midway through a solemn, 44-minute ceremony only steps from the site of the assassination on November 22, 1963.
Kennedy, the 35th president of the United States who served less than three years, is often ranked among the nation's most revered presidents.
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The Dallas event was designed to be a delicate balancing act of honouring Kennedy's memory without sensationalising his murder, and to help the city throw off its reputation as "the city that killed Kennedy".
It opened with a video from an organiser speaking of that goal, and continued in Rawlings remarks, which keyed off Kennedy's call for the United States to embrace and conquer a new frontier of challenges.
A new JFK monument also was unveiled, in the infamous section of land known as the "grassy knoll".
"A new era dawned and another waned a half century ago when hope and hatred collided right here in Dallas," Dallas Mayor Mike Rawlings said in his remarks commemorating Kennedy's death.
Rawlings then read the final words of the speech Kennedy was to deliver that day. That was followed by a moment of silence at 12:30 pm, the time Kennedy was shot a few feet from where Rawlings spoke.
In Boston, Gov Deval Patrick took part in a wreath-laying ceremony at the Kennedy statue on the front lawn of the Statehouse.
Earlier Friday, at Arlington National Cemetery in Virginia, Jean Kennedy Smith laid a wreath at her brother's grave.
The last surviving Kennedy sibling, Smith was accompanied by about 10 other members of the Kennedy family.
Yesterday's remembrance extended across the ocean to Kennedy's ancestral home in Ireland, where a half-dozen Irish soldiers formed a guard of honour outside the US Embassy as the American flag was lowered to half-staff.