The singer took home three gongs for 'Best Female', 'Biggest Fans' and 'Best Song' for her single 'Born This Way', as well as performing track 'Marry the Night' at the ceremony.
Upon receiving the 'Best Song' award from Hayden Panettiere, GaGa said: "I knew that this song was very special when I wrote it... I just didn't know how special it would be. I love you Little Monsters, until the end!"
Panettiere was briefly interrupted by a streaker as she prepared to announce the winner of the award.
Other winners included Bruno Mars, who was handed trophies in the 'Best New' and 'Best Push' categories, while 'Firework' singer Katy Perry has taken home the 'Best Live' award.
> MTV EMAs - winners in full
Justin Bieber, whose girlfriend Selena Gomez hosted tonight's event, was given the award for 'Best Male' and 'Best Pop'.
On accepting the latter, Bieber alluded to Mariah Yeater's recent claim that he fathered her baby, saying: "There's been a lot of crap on the internet lately."
Eminem was crowned with the 'Best Hip-Hop' award, while Adele was given the 'Best UK & Ireland Act' gong.
Linkin Park have been named 'Best Rock', while Thirty Seconds to Mars came away with awards for both 'Best Alternative' and 'Best World Stage'.
The ceremony also saw performances from Coldplay, Bruno Mars, LMFAO, Selena Gomez and Jessie J.
> MTV EMAs - performances and awards in pictures
> MTV EMAs - pictures from the red carpet
Look through our gallery below to see highlights from the show: