"He changed the world!! A true visionary. What a loss. I'm devastated," Madonna wrote on Instagram, where she posted a picture of herself with the Purple One.
Madonna had a tumultuous relationship with Prince. They briefly dated in the 1980s before a long feud that they had since resolved.
Prince, a legendary guitar player, performed on her 1989 "Like a Prayer" album, with the track "Love Song" recorded at his Paisley Park studio where he died.
Madonna included a lyric from the track in her Instagram post: "This is not a love song."