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It won both record and song of the year, becoming the first hip hop track to win either of the top Grammy categories in 61 years. "This is America" also took Grammys for best music video and best rap performance.
However, Childish Gambino, the music alter ego of actor Donald Glover, was not around to accept the honor.
Both Glover and leading nominee Kendrick Lamar were Grammy no-shows in what was seen as a snub by the rappers for past disappointments when socially incisive rap material lost out to pop or R&B at the highest honors in the music business.
"I really wish he (Glover) was here right now. All of this was his vision and he deserves this credit," said songwriter Ludwig Goransson, who worked with Glover on the track.
"It speaks to people, it calls out injustice, celebrates life and reunites us all at the same time," Goransson said, accepting the award on Glover's behalf.
The album of the year Grammy went to Musgraves for "Golden Hour," reflecting a show and a year that was dominated by female performers and winners across multiple genres.
"I would have nothing without songs. It's all about the songs," said Musgraves, who also won three other Grammys.
SPRINGING A SURPRISE
Popular rapper Cardi B, who wore a black and silver mesh body suit to perform her song "Money," won her first Grammy, taking best rap album for "Invasion of Privacy."
The outspoken New Yorker seemed uncharacteristically overwhelmed by the win.
"Ooh. The nerves are so bad," she said, accepting her Grammy. "Maybe I need to start smoking weed."
Lady Gaga won three trophies and British pop singer Dua Lipa was named best new artist. Canadian rapper Drake, who was also not expected to show up, made a surprise appearance to accept the Grammy for best rap song for "God's Plan."
Drake, the biggest streaming artist of 2018, told musicians not to worry about winning prizes.
"The point is you've already won if you have people who are singing your songs word for word, if you're a hero in your hometown," Drake said in his acceptance speech.
"If there's people who have regular jobs who are coming out in the rain and the snow and spending their hard-earned money to buy tickets to come to your shows, you don't need this right here, I promise you," he said.
Music, old and new, ruled in a live telecast that was largely politics-free, in contrast to U.S. awards shows in the past two years.
Hosted by Alicia Keys, the show featured rousing performances by Lady Gaga, Cardi B, Jennifer Lopez, Diana Ross, Camila Cabello, Dolly Parton, Miley Cyrus, Janelle Monae and Katy Perry, as well as a tribute to the late Aretha Franklin.
The Grammys sprang another surprise by bringing on former U.S. first lady Michelle Obama for an opening segment in which she joined Lady Gaga, Keys, Lopez and actress Jada Pinkett Smith to talk about the power of music.
"From the Motown records I wore out on the (Chicago) Southside to the 'Who Run the World' songs that fueled me through this last decade, music has always helped me tell my story," Obama told the cheering celebrity audience in Los Angeles.