The 50-year-old Aniston was seen blushing after her close friend DeGeneres, 61, went for a lip-to-lip in the upcoming episode of her talk show, reports dailymail.co.uk.
The kiss comes two weeks after DeGeneres planted a firm smooch on radio personality Howard Stern's mouth, also on her show.
"Did you enjoy it? How was it? Were you nervous? Did you kind of get into it?" Aniston asked DeGeneres.
Replied DeGeneres, who has been married to actress Portia de Rossi since 2008: "It was... it was pleasant," .
It all started when Aniston quizzed DeGeneres on kissing Howard Stern. "When was the last time you kissed a guy?" she asked.
DeGeneres replied: "Why is everyone so shocked? I kiss guys, I kiss guys like that, I don't make out with guys but I kiss guys on the lips.
In return, she asked Aniston: "When was the last time you kissed a girl on the lips?"
"I don't kiss girls on the lips, no ..." replied Aniston, hesitantly.
It was at that point that DeGeneres leaned over and smooched Aniston.
As the studio audience went wild, the TV personality laughed: "That's what they wanted to see. They've been wanting that for years!"
Aniston told DeGenres she had "very soft lips", to which Ellen said: "So do you, that's why I do what I do (like women)!"
She added: "No razor burns, soft lips," to which Aniston sagely replied: "I get it."
In an earlier episode of "The Ellen DeGeneres Show" earlier this month, Howard Stern had proposed the idea of a kiss in order to distract audience attention from the controversy that DeGeneres has been dealing with ever since she was pictured watching a Dallas Cowboys home game with former president George W. Bush.
( With inputs from IANS )