The 'Super Bass' singer, who opened the awards show with David Guetta earlier in the evening, took home the accolade for 'Favourite Rap/Hip-Hop Artist'.
Minaj, clad in an enormous green dress, had to be helped on stage to accept the award.
"Oh my god, you guys," she said. "There's so much love in this room."
She continued: "I didn't think I was going to win it."
The singer went on to thank God, as well as four others, including Taylor Swift, for convincing her to release 'Super Bass'.
Minaj beat male rap/hip-hop artists Lil Wayne and Kanye West to the award.
The star later took home the prize for 'Favourite Rap/Hip-Hop Album' for Pink Friday, tweeting after the show: "I'm still in shock. The audience was so DOPE!!!
"My barbz & I have come such a long way. 2 AMA's??? God is good right barbz??? *kisses u then mushes u* :p (sic)"
The 2011 American Music Awards aired on ABC and will air in the UK on November 26 at 10pm on VIVA.
More from the American Music Awards 2011:
> Enrique Iglesias performs with high school choir at American Music Awards 2011
> Justin Bieber performs 'Mistletoe' at American Music Awards 2011
> Taylor Swift takes home 'Favourite Country Female Artist' at AMAs 2011
> American Music Awards 2011: Full list of winners as they are announced