The British songstress won a total of 12 prizes at the prestigious Las Vegas ceremony, including Top Artist and Top Female Artist.
Adele's record-breaking album '21' garnered the star a wealth of honours, such as Top Pop Album, Top Digital Media Artist and Top Billboard 200 Album.
From a completely different genre, LMFAO also won big time, taking home six trophies, including Top/Duo Group and Top Hot 100 Song for their hit 'Party Rock Anthem'.
Taylor Swift won Woman of the Year, while Lil Wayne was awarded as Top Male Artist.
The night saw performances from the biggest names in pop, including Katy Perry and Justin Bieber.
The music awards show also paid tribute to a number of music legends who have recently passed away. In an emotional homage to late Whitney Houston,k Jordin Sparks performed her hit 'I Will Always Love You', while Whitney's daughter Bobbi Kristina Brown was seen tearing up in the audience.
Bobbi later accepted the Millennium Awards on behalf of her mother. She was joined on stage by Whitney's sister-in-law, Pat Houston.
"I really want to say thank you to everyone who supported us through it all. Not just from when it was good but when it was bad, too. Thank you for showing that much love, because she deserved it... I'm just blessed to have been in such an incredible woman's life. There will never be another one, ever," Bobbi said.
Donna Summer - who died of lung cancer last week - was also honoured. Natasha Bedingfield sang the late singer's hit Last Dance in memory of the star, while Cee Lo Green performed the Beastie Boys' (You Gotta) Fight for Your Right (to Party!) in remembrance of MC Adam Yauch, who passed away earlier this month.
Sad news also broke of Bee Gees legend Robin Gibb's death last night.
"His voice and music of the Bee Gees will live on forever," Julie Bowen, the show's co-host said.
The singer passed away after a long battle with cancer.
List of winners:
Social Artist of the Year - Justin Bieber
Top Artist - Adele
Woman of the Year - Taylor Swift
Top Female Artist - Adele
Top Billboard 200 Artist - Adele
Top Hot 100 Artist - Adele
Top Digital Songs Artist - Adele
Top Radio Songs Artist - Adele
Top Streaming Artist - Rihanna
Top Digital Media Artist - Adele
Top Pop Artist - Adele
Top Country Artist - Lady Antebellum
Top Alternative Artist - Coldplay
Top Latin Artist - Shakira
Top Christian Artist - Casting Crowns
Best New Artist - Wiz Khalifa
Top Duo/Group - LMFAO
Top Male Artist - Lil Wayne
R&B Artist of the Year - Chris Brown
Top Rock Artist - Coldplay
Top Touring Act - U2
Top Dance Act - Lady Gaga
Top Billboard 200 Album - 21 by Adele
Top Pop Album - 21 by Adele
Top R&B Album - 4 by Beyoncé Knowles
Top Rap Album - Tha Carter IV by Lil Wayne
Top Country Album - My Kinda Party by Jason Aldean
Top Rock Album - Mylo Xyloto by Coldplay
Top Alternative Album - Mylo Xyloto by Coldplay
Top Latin Album - Formula: Vol. 1 by Romeo Santos
Top Dance Album - Born This Way by Lady Gaga
Top Christian Album - Come To The Well by Counting Crowns
Hot 100 Song of the Year - Party Rock Anthem by LMFAO
Top Rock Song - Pumped Up Kicks by Foster The People
Top Digital Song - Party Rock Anthem by LMFAO
Top Radio Song - Give Me Everything by Pitbull Feat. Ne-Yo, Afrojack & Nayer
Top Streaming Song (Audio) - Rolling in The Deep by Adele
Top Streaming Song (Video) - Super Bass by Nicki Minaj
Top Pop Song - Party Rock Anthem by LMFAO
Top R&B Song - Motivation by Kelly Rowland & Lil Wayne
Top Rap Song - Party Rock Anthem by LMFAO
Top Country Song - Dirt Road Anthem by Jason Aldean
Top Alternative Song - Rolling in the Deep by Adele
Top Latin Song - Danza Kuduro by Don Omar & Lucenzo
Top Dance Song - Party Rock Anthem by LMFAO
Top Christian Song - Blessings by Laura Story
Icon Award - Stevie Wonder
Spotlight Award - Katy Perry
Millennium Award - Whitney Houston
Battle of The Bands Dreamseeker Artist of the Year - Patent Pending
Tagged in Adele Whitney Houston Robin Gibb LMFAO Donna Summer