The star, who died last January, was awarded best British male and best British album, for his mournful swansong, Blackstar.
His victory meant that grime artists left without any trophies, despite a breakthrough year for the genre.
However, Skepta stole the show with a blazing performance of Shut Down.
South London MC Stormzy also joined Ed Sheeran on stage for a new version of his single Shape Of You; while Emeli Sande, the soul star who started out singing on tracks by Wiley and Chipmunk, won best British female.
Rag 'N' Bone man was the other big winner of the night taking home two awards - the critics choice award and best British breakthrough act.
Bowie's wins were a fitting tribute to one of Britain's most influential and groundbreaking musicians.
Collecting the best album prize, his son the film director Duncan Jones spoke about the star's enduring legacy.
"He's always been there supporting people who think they're a little bit weird or a little bit strange. He's ways been there for them.
"This award is for all the kooks and all the people who make the kooks," he said, referencing the song his father wrote for him as a child, from the Hunky Dory album.
As well as honouring Bowie, the Brits paid tribute to George Michael, who died on Christmas day.
His former Wham! bandmates Andrew Ridgeley, Pepsi and Shirlie, made an emotional speech, saying: "His beautiful voice will live on forever as a gift to us all."
Coldplay's Chris Martin then sang an understated but moving version of Michael's A Different Corner, duetting with a recording of the star's own voice.