Celebrities including Tom Hanks, Robert De Niro and Michael Jordan were also among the 21 recipients of the Presidential Medal of Freedom.
Barack Obama said it was easy to forget the risk Ellen De Generes took to come out as gay in 1997.
He said her bravery helped "push our country in the direction of justice".
"It's easy to forget now, when we've come so far... just how much courage was required for Ellen to come out on the most public of stages almost 20 years ago," he said during the award ceremony at the White House.
"What an incredible burden that was to bear - to risk your career like that - people don't do that very often. And then, to have the hopes of millions on your shoulders."
The award, which recognises contributions to United States culture, security and international interests, is the highest honour a civilian can receive, alongside the Congressional Gold Medal, a similar accolade awarded by the US Congress.
"These are folks who have helped make me who I am,'' Obama said.
"Everybody on this stage has touched me in a very powerful, personal way, in ways that they probably couldn't imagine."
Honourees from the entertainment world included actors Tom Hanks, Robert DeNiro, Robert Redford and Cicely Tyson, as were musicians Bruce Springsteen and Diana Ross.
From the sporting world, former basketball superstars Kareem Abdul-Jabbar and Michael Jordan - who President Obama jokingly referred to as "the guy from Space Jam"- were awarded the medal, alongside sports broadcaster Vin Scully.
Bill and Melinda Gates were awarded for their philanthropic work through their charitable foundation.
Despite the president's words on the contribution Ellen De Generes made to the country, she almost missed the ceremony after security refused to let her in to the White House.
"They haven't let me in to the White House yet because I forgot my ID," she tweeted, alongside a photo of herself sitting on a nearby park bench.
Once inside, however, she took advantage of the assembled icons to film a take on the mannequin challenge.
Other recipients of the Presidential Medal of Freedom were:
- Richard Garwin, an inventor and physicist who made contributions to the nation's defence
- 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
- Eduardo Padron, president of Miami Dade College
- Posthumous honours went to Native American advocate Elouise Cobell and Rear Admiral Grace Hopper