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Bieber's wins included the show's top award, artist of the year. His mom joined him onstage as he collected the trophy, beating out Rihanna, Maroon 5, Katy Perry and Drake.
"I wanted to thank you for always believing in me," Bieber said, looking to his mom.
The 18-year-old also won the honour in 2010. He said: "It's hard growing up with everyone watching me" and asked that people continue to believe in him.
Bieber and Nicki Minaj performed together - and separately - at the AMAs, and were both multiple winners.
PSY vs Hammer
But another collaboration was the night's most colourful performance: Korean rapper PSY and MC Hammer. Hammer joined the buzzed-about pop star for his viral hit Gangnam Style.
PSY rocked traditional "Hammer" pants as they danced to his jam and to Hammer's Too Legit to Quit.
Bieber won favourite pop/rock male artist in the first award handed out at Sunday's show and gave a shout-out to those who didn't think he would last on the music scene.
"I want to say this is for all the haters who thought I was just here for one or two years. I feel like I'm going to be here for a very long time," he said.
He also won favourite pop/rock album for his platinum-selling third album, Believe. He gave a stripped down, acoustic performance of As Long As You Love Me, then transitioned to the dance-heavy Beauty and a Beat, where Minaj joined him onstage.
Nicki Minaj's show-stealing ways
Minaj, who wore three different wigs and four outfits throughout the night, repeated her AMAs wins from last year, picking up trophies for favourite rap/hip-hop artist and album for Pink Friday: Roman Reloaded.
She was in an all-white get-up, including fur coat and pink hair when she performed her new song Freedom. The scene was ghostly and snowy, as a choir - also in white - joined her onstage. One background singer stole the performance, belting semi-high notes as Minaj looked on.
'So delicious'
As Bieber won his second award, he was kissed on the neck by Jenny McCarthy, who presented the award.
"Wow. I feel violated right now," he said, laughing.
"I did grab his butt," McCarthy said backstage. "I couldn't help it. He was just so delicious. So little. I wanted to tear his head off and eat it."
Bieber's red and black outfit seemed to be the night's theme, as Taylor Swift and Usher wore similar ensembles.
Other winnersDick Clark, who created the AMAs, was remembered by Ryan Seacrest and an upbeat performance by Stevie Wonder.
"What a producer he was," said Seacrest, as Wonder sang his hits, including My Cherie Amour.
Carly Rae Jepsen, who performed early in the night, won favourite new artist.
"I am floored. Wow," she said, thanking Bieber and his manager, Scooter Braun.
Party girl Ke$ha was glammed up on the red carpet, rocking long, flowy blonde hair and a light pink dress. She switched to her normal attire when she performed her hit single Die Young.
Kelly Clarkson also hit the stage, making a nod to her American Idol roots with a number on her dress and three judges looking on as she sang Miss Independent. Then she went into Since U Been Gone, Stronger and Catch My Breath.
Fellow Idol winner Carrie Underwood won best favourite country album and performed, hitting the right notes while singing Two Black Cadillacs.
Luke Bryan won favourite country male artist and Lady Antebellum favourite country group.
Sales, airplay and votes
American Music Awards nominees were selected based on sales and airplay, and fans chose the winners by voting online.
"What makes the American Music Awards special is the fans choose the winning artists," said Chester Bennington of Linkin Park, who won favourite alternative rock artist and performed Burn It Down.
David Guetta won the show's first-ever electronic dance music award.
