Lady Gaga's hit song "Shallow" from the movie "A Star is Born" won two Grammys, while the musician-turned actress took a third Grammy home for her "Joanne (Where Do You Think You're Going)", which won for pop solo performance.
Obama, who got a rousing applause from the crowd, so much so that she had to pause saying her lines and restart once it calmed, said music "fueled" her through the last decade.
"Shallow" won the Grammy for Best Song Written for Visual Media and was nominated for Record of the Year and Song of the Year.
Tori Kelly, who debuted on the music scene as a pop singer, won two awards for her first gospel album.
In a charming twist, USA president Jimmy Carter won his third Grammy in the Spoken World Album category for the audio version of his best-selling book "Faith: A Journey For All".
By downloading the app, you can also stream the Grammys from your phone or tablet.
Janelle Monae remembers being frustrated last year, but this year she is looking forward to the show, where women are now leading in nominations for big categories like album of the year and best new artist. "If there is people who have regular jobs who are coming out in the rain, in the snow, spending their hard-earned money to buy tickets to come to your shows, you don't need this right here, I promise you, you already won".
After her second, for the song named after the superstar's aunt, Lady Gaga called the award "more than me & my family could ever dream of".
Top nominees Gaga, Monae, Cardi B, Carlile and country star Kacey Musgraves are all due to take the stage at the Staples Center. Her performance sent Twitter abuzz.
What will the final speech from Neil Portnow - who caused more than a little consternation previous year when he said women needed to "step up" in order to secure broader inclusion - contain?
Diana Ross, who used her performance to mark her 75th birthday, also got the crowd up with hands in the air.
Several big stars are not attending the Grammys, including Grande, Taylor Swift, Kendrick Lamar, the top nominee with eight, and Drake, nominated for seven awards. Yolanda Adams, Fantasia and Andra Day will honour the late Aretha Franklin with a performance.