The 19-year-old star, famed for his on-stage athleticism, overshadowed Alicia Keys, who led the field with five nominations, and ended up with a pair of statuettes.
Brown was clearly shocked when his name was announced for artist of the year, the ceremony’s final award.
"I probably was shocked like everybody else," Brown told reporters backstage at the Nokia Theater. "I know everybody was like, ‘Huh?’ I thought Coldplay should have genuinely won that award, but I’ll take it!"
He was also named favorite male artist in both the soul/R&B and pop/rock categories. His girlfriend, Rihanna, won those categories for the women, beating Keys in both races.
Keys’ awards were for her chart-topping disc, "As I Am," which was named favorite album in the soul/R&B and pop/rock categories.
Behind Keys in the nominees list were British rock band Coldplay and American country-rock veterans the Eagles, who both went home empty-handed.
Other multiple winners included outspoken rapper Kanye West, who has never been afraid to express his dismay when he is overlooked at awards shows. He won the first two American Music Awards of his career, but said he would give one of them away to fellow nominee, Lil Wayne.
"If it was last year, this would have been my award," he said of the favorite male rap/hip-hop category. "This year, it’s Wayne’s award. We’ll see what happens next year."
Earlier, he won for the statuette for favorite rap/hip-hop album with "Graduation." West challenged musicians of all genres to push each other, and to reclaim the spirit of artists like the Beatles, Jimi Hendrix and Led Zeppelin. In his case, he declared, "I wanna be Elvis!"
But host Jimmy Kimmel retorted a little later, "Elvis died on the toilet with half a jelly donut in his mouth, so you might want to rethink that one."
Kimmel also took a dig at addiction-plagued rocker Scott Weiland, who had to struggle to introduce a performer. Kimmel suggested that Disney starlet Miley Cyrus, who turned 16 on Sunday, would now be able to drive him home.
Among the first-time winners were Taylor Swift, current holder of the No. 1 spot on the U.S. pop album chart with her album "Fearless." She appeared to be the only shocked person in the Nokia Theater room when she was named favorite female country singer.
"It’s an honor that you even care about the songs I wrote in my bedroom," said the 18-year-old star.
Another country star, Brad Paisley, was also a first-time winner, in the genre’s favorite male artist category.
I have always, always wanted to win an American Music Award," he said, pausing to survey the bottom of his perspex statuette. "Made in China?"
For the second year, winners were determined by online voting. They used to be decided by a poll of 20,000 music buyers, but producers decided to make the event more inclusive in the wake of slumping ratings. The move seemed to work, with last year’s show attracting 11.8 million viewers, up from 10.9 million the year before.
The performance-heavy event spanned the generations, from Cyrus to former Eurythmics singer Annie Lennox, who earned a standing ovation with her heartfelt piano ballad "Why."
The Scottish rocker received a lifetime achievement award and said, "I never thought that I would live to see the day that I would be 53 years old standing on the stage."