She sang in public for the first time since her vocal cord surgery last year, which had forced her to pull out of all appearances for the final few months of 2011 while she rested following the operation.
Adele sang 'Rolling in the Deep' and received a standing ovation from the star-studded audience.
[Related feature: Grammys 2012 on-stage photos]
[Related feature: Grammys 2012 red carpet fashion]
She picked up song of the year and record of the year for the track, as well as best pop solo performance for 'Someone Like You'.
When she collected that award, she said: "I can't believe I'm getting emotional already. And seeing as it's a vocal performance, I need to thank my doctors, I suppose, who brought my voice back."
[Related article: Grammys 2012: Katy Perry shows she's the queen of quirky]
Adele collected album of the year for 21 and said: "First of all I want to say mum: 'Girl did good.'
"This record is inspired by something that is really normal and everyone's been through it, which is a rubbish relationship. It's been a life changing year."
She also picked up best pop vocal album for 21, and won best short form music video.
The Londoner now matches Beyonce for the most awards won in one night by a female artist.
Foo Fighters and Taylor Swift also received multiple awards.
Mitch and Janis Winehouse joined Tony Bennett to accept the best pop duo/group performance award on behalf of the late Amy Winehouse, for her duet 'Body and Soul' with Tony.
Grammy Awards 2012 winners
Record of the Year — Rolling In The Deep, Adele
Album of the Year — 21, Adele
Song of the Year — Rolling In The Deep, Adele
Best New Artist — Bon Iver
Best Pop Solo Performance —Someone Like You, Adele
Best Pop Duo/Group Performance — Body And Soul , Tony Bennett & Amy Winehouse
Best Pop Vocal Album — 21, Adele
Best Dance Recording - Scary Monsters and Nice Sprites, Skrillex
Best Dance/ Electronica Album - Scary Monsters and Nice Sprites, Skrillex
Best Traditional Pop Vocal Album — Duets II, Tony Bennett & Various Artists
Best Rock Performance — Walk, Foo Fighters
Best Rock Song — Walk, Foo Fighters
Best Rock Album - Waiting Light, Foo Fighters
Best R&B Performance — Is This Love, Corinne Bailey Rae
Best R&B Song — Fool For You
Best R&B Album — F.A.M.E., Chris Brown
Best Rap Performance — Otis, Jay-Z and Kanye West
Best Country Solo Performance — Mean, Taylor Swift
Best Country Song — Mean, Taylor Swift
Best Short Form Music Video — Adele