The eccentric singer - who was nominated for a record 13 awards - took home an impressive eight trophies at the prestigious ceremony, including Video of the Year for 'Bad Romance'.
When accepting the main award - which was presented to her by Cher - an emotional Gaga said: "I was so nervous tonight that I'd let my fans down.
"I promised that if I won this tonight, I'd announce the name of my new record."
She then went on to tell the thrilled crowd her new album would be called 'Born This Way', before singing part of the title song.
The 24-year-old star also won prizes for Best Pop Video, Best Female Video and Best Collaboration - for her 'Telephone' duet with Beyonce Knowles - and she thanked her fans for their support.
She said: "Tonight, little monsters, we're The Cool Kids at the party."
Eminem - who won Best Male Video and Best Hip-hop Video - opened the show with 'Not Afraid', before teaming up with Rihanna for 'Love the Way You Lie', while Best New Artist winner Justin thrilled his fans with a performance of 'Baby' outside the Nokia Theater.
Troubled actress Lindsay Lohan - who has just completed court-ordered rehab treatment - appeared at the start of the show in a pre-recorded sketch, which poked fun at her lifestyle.
Talking about host Chelsea's self-confessed love of vodka, Lindsay quipped: "Pull it together! Do you think anyone wants to work with a drunk? Take it from me!"
Main winners at the 2010 MTV Video Music Awards:
Best Collaboration: Lady Gaga featuring Beyonce Knowles, 'Telephone'
Best Female Video: Lady Gaga, 'Bad Romance'
Best Male Video: Eminem, 'Not Afraid'
Best Hip-hop Video: Eminem, 'Not Afraid'
Best New Artist: Justin Bieber featuring Ludacris, 'Baby'
Best Pop Video: Lady Gaga, 'Bad Romance'
Best Rock Video: 30 Seconds to Mars, 'Kings and Queens'
Best Dance Music Video: Lady Gaga, 'Bad Romance'
Best Art Direction: Florence and the Machine, 'Dog Days Are Over'
Best Choreography: Lady Gaga, 'Bad Romance'
Best Cinematography: Jay Z and Alicia Keys, 'Empire State of Mind'
Best Direction: Lady Gaga, 'Bad Romance'
Best Editing: Lady Gaga, 'Bad Romance'
Best Special Effects: Muse, 'Uprising'
Best Breakthrough Video: The Black Keys, 'Tighten Up'
Video of the Year: Lady Gaga, 'Bad Romance'
It's taken nearly 10 years for filmmaker Robert Rodriguez and graphic novelist Frank Miller to...
It's all about revenge in Sin City now as the wounded (both physically and mentally)...
Where the 2011 reboot felt effortless in the way it recaptured that warmly anarchic Muppets...
The everlasting trail of violence, death and deceit continues with the return of several characters...
Robert Rodriguez returns to Grindhouse territory with this B-movie spoof sequel that mixes hilariously knowing...
Machete Cortez is a formidable former member of the Mexican Federal Police and happens to...