Obama presented the medal the highest award the US gives a civilian to entertainer Oprah Winfrey, former President Bill Clinton, and leaders from the worlds of sports, entertainment, science and public service.
The late Sally Ride, the first American woman in space, was awarded the medal posthumously.
Hillary Rodham Clinton and Steven Spielberg were among those gathered at the White House to watch the ceremony.
The ceremony marks the start of a day honoring Kennedy's legacy two days before the nation pauses to remember the 50th anniversary of his assassination. Later, Obama will pay a visit to the eternal flame that marks John F. Kennedy's gravesite. He'll be joined by first lady Michelle Obama and the Clintons at the ceremony at Arlington National Cemetery.
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Turning to the former White House inhabitant, Obama said that Bill Clinton's presidency had been only the start of his work to improve the world, crediting his post-presidency humanitarian works as helping to save or improve the lives of hundreds of millions around the world.
Obama said Ride, who died in July 2012, didn't just break the stratospheric glass ceiling, "she blasted right through it."
"Young girls need to see role models, she said. You can't be what you can't see," Obama said. "Today our daughters, including Malia and Sasha, can set their sights a little bit higher because Sally Ride showed them the way."