During her acceptance speech, a teary-eyed Gaga told the audience how important fashion was in her life growing up.
As a teenager, she'd save her money to buy vintage Thierry Mugler from a neighborhood thrift shop, checking in with the salesman regularly to make sure her favorite pieces hadn't sold while she was raising the cash. She planned her outfits for Friday night parties as if she was going to the Oscars, she said.
Other fashion fans attending the awards said Gaga deserved the award.
"I just like that she goes to the place that she wants to go every time, and it's always something new and unexpected, and she does what feels right for her," said actress and designer Ashley Olsen.
The two standing ovations of the night went to photographer Arthur Elgort and designer Marc Jacobs, who was there for his "half-lifetime achievement award," according to presenter Sofia Coppola.
"This achievement is born of love, passion, creativity ... and a hell of a lot of hard work," said Jacobs, who is 48.
He added, "I believe we all know and feel the greatest reward is the process itself."
The Associated Press contributed to this report.