The 21st annual prize presentation is to take place June 3 at the Gibson Amphitheatre.
"This MTV Movie Awards will be more impressive than 'The Avengers' and you won't have to wait an hour for someone to hulk out," Brand said in a statement.
"With his amazing ability to span the full spectrum of comedy from the most high- to low-brow, Russell's smart, unpredictable wit uniquely connects him to our audience," said Stephen Friedman, president of MTV. "His rock 'n' roll sensibility and fearlessness give us the perfect partner with whom to take a leap of faith with as we meld the worlds of movies and music together on one very special night."
Brand's film credits include "Forgetting Sarah Marshall," "Get Him to the Greek," "Despicable Me," "Arthur" and the upcoming "Rock of Ages."
In addition, Brand will soon headline a series of six half-hour late-night TV comedy specials to be recorded in front of a live audience on the FX network.