Drake took aim at the Recording Academy as he accepted the award for best rap song – appearing to describe the body as “a bunch of people who might not understand what a mixed race kid from Canada has to say”.
The Canadian rapper – who has had an ambivalent relationship with the Grammys in recent years – was honoured for his hit God’s Plan.
While accepting the gong, he appeared to aim a jibe at the Academy in charge of voting for the prizes, saying: “We play in an opinion-based sport, not a fact-based sport.”
The 32-year-old addressed the other rappers in his category, which included Cardi B, Travis Scott and Mac Miller, the hip hop artist who died last year of an accidental overdose.
“It’s not the NBA where at the end of the year you are holding a trophy because you made the right decision or won the game,” he told the audience at the Staples Centre.
“This is where, sometimes, it’s up to a bunch of people who might not understand what a mixed race kid from Canada has to say, or a fly Spanish girl from New York, or anybody else, or a brother from Houston.
“But the point is you have already won if you have people who are singing your songs word for word, if you’re a hero in your home town… I promise you, you’ve already won.”
Drake was cut off mid-sentence as he tried to add to his statement, but coverage cut away from the rapper and the sound of his voice faded.
Drake has now won two Grammys for best rap song after his track Hotline Bling took home the gong in 2017.
Outside of that category, Drake earned five nominations this year: record of the year, album of the year, song of the year, and best rap performance twice.
Earlier Lady Gaga and Bradley Cooper became the first acts to scoop a prize at the 61st Grammy Awards.
The pair won best pop duo/group performance for Shallow, the hit single from the musical drama film A Star Is Born, which stars Gaga as an emerging pop star and Cooper as an ageing rocker.
Accepting the prize on stage, Gaga paid tribute to Cooper, who could not attend due to being in London for the Bafta film awards ceremony earlier in the evening.
She said: “I wish Bradley was here with me right now. Bradley, I loved singing this song with you. If I don’t get another chance to say this, I just want to say I’m so proud to be a part of a movie that addressed mental health issues, they’re so important.”
Gaga also urged anyone who suspects someone may be struggling with their mental health to intervene.
She added: “If you see someone that’s hurting, don’t look away.”
Host Alicia Keys opened the 2019 Grammys with a show of girl power, introducing Gaga, Jennifer Lopez, Jada Pinkett Smith and Michelle Obama on stage.
The show had been criticised last year for its lack of female nominees after women were largely ignored in the major categories.
It was markedly different his year, with five of the eight album of the year nominees being female.
To huge cheers, Obama, the wife of former US president Barack Obama, addressed the crowd.
She said: “Music has always helped me tell my story and I know that’s true for everyone here.”
Obama added: “Music helps us share ourselves, our dignity and sorrows, our hopes and joys. It allows us to hear one another to let each other in.”
Camila Cabello, who was nominated for three awards, opened the show with a lively performance of her hit single Havana along with rapper Young Thug, before Ricky Martin joined them on stage.
Earlier, during the Grammy Awards Premiere event, the Arctic Monkeys missed out on the best alternative music album for their effort Tranquility Base Hotel + Casino.
The prize instead went to American singer-songwriter Beck for Colours.
Best music video was awarded to Childish Gambino, also known as Donald Glover, for the politically charged visual counterpart to his hit single This Is America.
Quincy, the documentary about revered US musician Quincy Jones, was named best music film.
Pop solo performance was awarded to Gaga for Joanne (Where Do You Think You’re Goin’?) while pop vocal album went to Ariana Grande for Sweetener.
It was Grande’s first Grammy win and writing on Instagram, she described it as “wild and beautiful”.
She also addressed her row with the Recording Academy which led to her not appearing at the ceremony, telling fans, “I tried and still truly wished it had worked out”.
Producer of the year went to Pharrell, who won ahead of Kanye West.
Rapper Cardi B referenced the hit film Black Panther during a typically elaborate performance.
Midway through her song, she flashed the Wakanda Forever sign from Marvel’s superhero blockbuster film.
Her performance came before the award for best country album was handed to Kacey Musgraves for Golden Hour.
The night’s first performance peak came when Miley Cyrus and Katy Perry performed alongside Dolly Parton in a tribute to the revered country star.
Nine-time Grammy winner Parton, 73, defied her age to belt out classics Here You Come Again, Jolene and 9 To 5, as well as a cover of Neil Young’s After The Gold Rush.
Parton was joined on stage by Perry and Musgraves for Here You Come Again, before bringing out her goddaughter Cyrus for a duet of Jolene.