E!Online reported Gaga took the honors for Best Song, Best Video, Best Female and Biggest Fans.
"Thank you for believing in my vision," she told the audience. "The success of 'Born This Way' has changed my life."
Canadian teen sensation Justin Bieber won for Best Male and Best Pop.
Both he and Gaga also performed songs during the evening.
Katy Perry won Best Live Performer. Other winners included Eminem for Best Hip-Hop, Bruno Mars for Best New Act and Best Push Act, Linkin Park for Best Rock, and Thirty Seconds to Mars as Best Alternative and Best World Stage Performance.
The festivities included a naked man showing up on stage as actress Hayden Panettiere was getting ready to present Gaga the award for Best Song, the Mirror reported.
"Dude, what are you doing?" she asked him.
He answered he thought he'd "do a streak."
Gaga didn't mention what apparently was a scripted sketch when she accepted her award.