The 49th Annual American Music Awards were held on November 21, 2021, at the Microsoft Theater in Los Angeles, recognizing the most popular artists, singles and albums of 2021. Cardi B hosted the ceremony, following Queen Latifah (1995) as the only female rappers in history to do so. Cardi B became the first artist to win Favorite Rap/Hip Hop Song three times. BTS, Doja Cat, and Megan Thee Stallion won three awards each.
The ceremony was notable as the first produced under the banner of MRC Live & Alternative, which was formerly known as **** Clark Productions after use of that name was phased out the month before. However, this would turn out to be the only year produced under this banner, as the **** Clark Productions name was restored in August 2022.