They picked up several of the top awards, including best male and best female act.
Lady Gaga also won for best song and best video for "Born This Way." Bieber picked up best pop act as well.
After he won his second award, Bieber praised his fans for staying with him despite "a lot of crap on the Internet," an apparent reference to unsupported allegations that he had fathered a child after a brief liaison.
The awards were held in Belfast, Ireland for the first time and included a video tribute to the late Amy Winehouse.
American band Thirty Seconds to Mars won for best alternative act and best world stage. Katy Perry took home the prize for best live act and Linkin Park won for best rock artist.
Eminem took top honors in the hip-hop category, and the best new artist award went to Bruno Mars.
The band Queen received the "Global Icon" award, in effect a lifetime achievement award to the now-graying rockers, who closed the show with a spirited set of their classics, including "We Will Rock You" and "We Are the Champions."
The Associated Press contributed to this report.