The singer`s empowering track `Firework` was given the biggest award of the evening, which she accepted wearing a multi-coloured dress and with a bright yellow cube on her head.
As she collected the trophy - nicknamed a Moonman - Katy said: "Oh my goodness! Thank you so much. This is my second Moonman. I`m very proud of the song it stands for, which is `Firework.`
"I feel like I am doing something right when I sing that song. So thanks to everyone who helped to create it."
Katy`s track `E.T.` - which features Kanye West - later picked up two awards for Best Collaboration and Best Special Effects.
Adele was the biggest winner of the night, taking home four trophies for her single `Rolling in the Deep`: Best Art Direction, Best Cinematography, Best Direction and Best Editing.
Lady Gaga was the recipient of a new award, Best Video With A Message for `Born This Way` and she appeared at the ceremony - held at the Nokia Theatre in Los Angeles - as her chain smoking male alter ego, Jo Calderone.
Accepting her award she said: "Earlier tonight they told me I got best video with a message. There are so many great artists in this room.
Every video they`ve got has a- message."
Earlier Gaga had opened the show, performing `You and I` with Queen guitarist Brian May.
Other stars to appear on stage included Beyonce Knowles - who had earlier revealed she is pregnant - her husband Jay-Z, who performed new single `Otis` with Kanye West, and Chris Brown.
The show also featured a tribute to Amy Winehouse - who unexpectedly died last month at the age of 27 - led by Russell Brand and Tony Bennett.