"Music shows us that all of it matters -- every story within every voice, every note within every song," said the former first lady, looking glam in a sparkling gunmetal pantsuit with a 1970s-esque wrap jacket.
"Is that right, ladies?" she said to resounding applause.
The Recording Academy behind the awards gala has faced a barrage of criticism for not embracing diversity within its ranks, after nearly muting women nominees at the show last year.
This year, five of the eight nominees for Album of the Year are women: rapper Cardi B, folk-rock singer Brandi Carlile, pop futurist Janelle Monae, R&B prodigy H.E.R. and country star Kacey Musgraves.
"Thank you so much, ladies, for your light, your message of love, your sisterhood," said Keys, the first woman to helm the show in 14 years.
"Give it up for these magnificent goddesses!" said Keys.