She sang a medley of hits in a shaky off-key voice (was Gaga nervous?) and seemed worried about a potential wardrobe malfunction tugging repeatedly at the heavily embellished fabric of her black off-the-shoulder jumpsuit.
The multi-platinum entertainer then changed into something more comfortable, overcame her jarring entrance and sat down with the daytime diva to discuss fashion, creative inspiration and the tragedy in Haiti.
In no time the queen of pop and the queen of all media were on a cozy first name basis. "Call me 'Gaga,'" the performer told her host. "If feels weird when people call me 'Lady.'"
Befitting their summit, the two power women exchanged gifts. Gaga gave Oprah a "hair" bow as well as a pair of Jean Paul Gaultier sunglasses, which she presented back stage in Chicago.
In exchange, Oprah treated Lady Gaga, "a serious foodie" to a homemade southern breakfast of fried chicken and waffles prepared by Art Smith, the talk show host's personal chef.
Appearing starstruck, Lady Gaga gushed, "You are the most amazing person in the world."
Gaga -- who was preceded on Friday's live show by "Avatar's" billion dollar man, director James Cameron -- told Oprah she was jealous of his film project because it incorporated one her fashion fantasies: "I always wanted to paint myself blue, but then 'Avatar' came out. He beat me to it."
The entertainer walked Oprah through her favorite avant garde fashion moments, beginning with the first performance her parents witnessed at a New York City club. "I was wearing a leopard g-string and an Indian headdress. My father was worried. I don't think that he got it."
And the singer explained the red dress she wore last year to meet Queen Elizabeth II as "my homage to the queen, but it was made out of latex so it's still Gaga." One of her zanier getups, a Kermit the Frog jacket and matching hat, was a deliberate fashion statement. "I don't like to wear fur. So I wanted people to look at Kermit and think about that."
Then she treated the audience to a behind-the-scenes look at her backstage fashion. "All my songs have their own wardrobe," she explained. "I really like shoulder pads and a lot of my outfits have them."
She took credit for creating the "disco bra" she wore in her "Just Dance" video and teased the audience saying, "I won't tell you my bra size though." She also confessed her bargain fashion obsession, "I love stripper shoes. So we buy very inexpensive ones and embellish them."
The show began on a serious note when Oprah conferred with CNN anchor Anderson Cooper via satellite from Haiti. Later, Lady Gaga said the earthquake hit home. "I was in New York during 9/11 and that does not compare to what these people are experiencing," she explained.
She announced she will donate all profits from her Jan. 24 Monster Ball as well as profits from related sales that day to earthquake relief efforts. For more details visit her official site.
And see which beauty product you can purchase to help Haiti.