The Kennedy Center is awarding DeGeneres the Mark Twain Prize for American Humor. The show will be broadcast Oct. 30 on PBS stations.
"Thanks to everyone at PBS. I am so happy to be part of your farewell season," DeGeneres joked in accepting the prize and taking a jab at Republican presidential candidate Mitt Romney's plans to stop funding public broadcasting.
On the red carpet before the show, DeGeneres said she doesn't see herself as political with her comedy, though, even though she's been a trailblazer.
"I just want to make people happy and make people laugh," she said.
DeGeneres, 54, began her career as a comedy club emcee in her native New Orleans. After a performance on Johnny Carson's show in 1986, he invited her over to his desk to chat. She was the first female comedian to receive that invitation from Carson.
Turning to acting, DeGeneres landed sitcoms on Fox and ABC, eventually starring in "Ellen" from 1994 to 1998. She broke new ground and a taboo in 1997 when she came out publicly as a lesbian and her TV persona then became the first lead character on prime-time TV to reveal she was gay. A record 46 million viewers watched the episode.
Coming out on TV 15 years ago feels like another life, she said Monday night before the show.
"I did it because it was the right thing for me to do," DeGeneres said. "It was the right thing for me to do to not live with shame. I happened to help a lot of people, and it happened to create a ruckus."
Jimmy Kimmel called it a milestone.
"For a lot of people, Ellen is their only homosexual friend," he said. "She's there in their living room every single day."
On stage, he said DeGeneres was his inspiration.
"Because of Ellen, in 1998, I mustered the strength to come out of the closet despite the fact that I'm not gay," he joked. "Thanks to Ellen, vests aren't just for magicians anymore."
Sean Hayes said DeGeneres made his former show, "Will and Grace," possible. He said her "fearlessness" was her biggest contribution and that she changed America.
"We didn't have a voice, until there was you," he said before breaking into a rendition of "Till There was You."
"Glee" star Jane Lynch said DeGeneres "took one for the team."
"She's the one who went in there with a machete" and cleared the way for other shows with gay characters such as "Glee," she said. "Look where she is today."
Kristin Chenoweth said DeGeneres has always remained kind.
"She's not a mean girl comic," she said.
When DeGeneres first heard she was receiving the same honor that Bill Cosby, Tina Fey and Will Ferrell won in recent years, she joked, "Why didn't I get this sooner?"
After DeGeneres came out on TV in 1997, the show began to tank and was canceled a year later. The feeling of rejection was enough to send DeGeneres into a depression. Still, "Ellen" paved the way for future shows to feature gay characters, from "Will and Grace" to "Modern Family."
DeGeneres came back with a CBS sitcom, movie roles and even a stint as an "American Idol" judge. Forbes magazine has ranked her as the 47th most-powerful woman in the world and estimated her earnings at $53 million last year.
Her hit talk show that debuted in 2003 is now in its 10th season. Among other achievements, that's where she eventually persuaded President Barack Obama to dance.
"She's brilliantly shined a light on society, and that's what Mark Twain did," said Cappy McGarr, an executive producer for the Mark Twain Prize show, when the award was announced.
The prize honors comedians in Mark Twain's tradition of satire and social commentary. Past winners include Steve Martin, Lily Tomlin and Whoopi Goldberg.
John Leguizamo saluted DeGeneres and PBS for planning to air the show.
"How about that? A gay woman on PBS with public money and the Kennedys," he said. "It's like the tea party's worst nightmare."