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"These are folks who have helped make me who I am," Obama said as the celebration concluded in the White House East Room.
Among those getting the Presidential Medal of Freedom were actors Tom Hanks, Robert De Niro, Robert Redford and Cicely Tyson.
Michael Jordan and Kareem Abdul-Jabbar, two of the best basketball players ever, were also among the honorees.
Bruce Springsteen and Diana Ross were recognized for their music.
Other honorees included philanthropists Bill and Melinda Gates, comedian Ellen DeGeneres and broadcaster Vin Scully.
Obama said the people receiving the medal helped push America forward and inspired millions around the world.
The award recognizes especially meritorious contributions to the national interests of the United States, to its culture, or to other significant endeavors.
Posthumous honors went to Native American advocate Elouise Cobell and Rear Adm. Grace Hopper.
Others receiving the award included: Richard Garwin, an inventor and polymath physicist who made pioneering contributions to the nation's defense; Frank Gehry, one of the world's leading architects; Margaret H. Hamilton, a mathematician and computer scientist; Maya Lin, the designer of the Vietnam Veterans Memorial; Lorne Michaels, producer of "Saturday Night Live"; Newton Minow, a former Federal Communications Commission chairman devoted to numerous public and charitable causes; and Eduardo Padron, president of Miami Dade College.
But the ceremony didn't completely go off without a hitch. DeGeneres tweeted that she had forgotten her ID, and wasn't allowed to enter the White House.
But after a few more well-placed tweets, she joined the party.
Obama provided introductions to each recipient, which included some of the contributions they've made to society.
"Since Jackie Robinson started at second base, Vin taught us the game and introduced us to its players. He narrated the improbable years, the impossible heroics, turned contests into conversations."
"Physically, intellectually, spiritually - Kareem is one-of-a-kind. An American who illuminates our most basic freedoms and our highest aspirations."
"He's inspiring our next generation through his advocacy for arts education in our schools...Frank's work teaches us that while buildings may be sturdy and fixed to the ground, like all great art, they can lift our spirits, they can soar and broaden our horizons."
"Today, every day in every way, Ellen counters what too often divides us with the countless things that bind us together, inspires us to be better - one joke, one dance at a time."
"America's dad has stood up to cancer with his beloved wife Rita, he's championed our veterans, supported space exploration, and the truth is, Tom has always saved his best roles for real life. He is a good man, which is the best title you can have."
"There is a reason you call somebody "the Michael Jordan of"...because Michael Jordan is the Michael Jordan of greatness. He is the definition of somebody so good at what they do that everybody recognizes it. That's pretty rare."
The Associated Press contributed to this report.