The Canadian hip hop artist will perform "Started From the Bottom," which MTV described as a "sinister-sounding" departure from earlier work, "filled with fire and frustration."
Since its release in February 2012, the song has been remixed by more than a dozen other rappers including Chris Brown.
Drake will join Justin Timberlake, Lady Gaga, Katy Perry and Kanye West on the VMAs stage. Robin Thicke and Miley Cyrus, both scheduled to perform, each have four award nominations.
MTV also confirmed Wednesday that Taylor Swift, Joseph Gordon-Levitt, Jared Leto and Selena Gomez, Emeli Sande and A$AP Rocky will be in attendance.
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