The band scooped up gongs for Best New Artist, Best Pop Video and Most Share-Worthy Video.
'The X Factor' 2010 contestants scooped up three prizes at the ceremony in Los Angeles, California.
The boys dedicated their Best Pop Video gong to their fans and joked about their clumsy ways after a mishap.
Niall told the audience: ''This one's for our fans, you're amazing. This one's for you.''
Liam joked: ''We've had this award two seconds and we've already broken it.''
Meanwhile, Louis took time out to thanks their boss and record company.
He said: ''Thanks to Simon Cowell and all at SyCo, this one's for our fans.''
The 2012 MTV Video Music Awards will air on Friday (07.09.12) at 9pm on MTV UK, Sky 126 and Virgin 311.
Full list of winners:
Best Video With A Message - Demi Lovato, 'Skyscraper'
Most Share-Worthy Video - One Direction, 'What Makes You Beautiful'
Best Electronic Dance Music Video - Calvin Harris, 'Feel So Close'
Best Pop Video - One Direction, 'What Makes You Beautiful'
Best Male Video - Chris Brown, 'Turn Up The Music'
Best Hip-Hop Video - Drake, 'HYFR'
Best Female Video - Nicki Minaj, 'Starships'
Best Rock Video - Coldplay, 'Paradise'
Best New Artist - One Direction, 'What Makes You Beautiful'
Video of the Year - Rihanna, 'We Found Love'