Walking out to a track by rapper Rick Ross, O'Brien joked that he was almost injured by the show's flashing pyrotechnics. "Fire, explosions and rap music: all things you associate with Conan O'Brien," he joked.
Jared Leto took home the award for best on-screen performance for his role in Dallas Buyers Club, which was presented by Lupita Nyong'o.
"A year ago nobody knew my name," quipped Nyong'o. "Now no one can pronounce my name."
Furthering the on-going speculation that Nyong'o and Leto are romantically linked, Leto, in a deep and suave tone, said, "It's an award in itself to get that from her."
Jonah Hill was awarded best comedic performance for The Wolf of Wall Street. His initial thanks went to all of his friends who he used to watch the show with back home before making it to the ceremony himself.
Early pre-show honours went to the Backstreet Boys for best musical moment, while the award for best cameo performance went to Rihanna for her appearance in the comedy This is the End. During the show, Rihanna was to take the stage with Eminem to perform their hit The Monster.
Best kiss awarded
Best kiss went to Emma Roberts, Jennifer Aniston and Will Poulter.
American Hustle and The Hobbit: The Desolation of Smaug topped the nominees on the two-hour show, where fans voted online for such zany awards as best villain. Jennifer Aniston from We're the Millers and Leonardo DiCaprio in The Wolf of Wall Street were vying for best shirtless performance.
Movie of the year nominees included 12 Years a Slave, The Hunger Games: Catching Fire, The Hobbit: The Desolation of Smaug, The Wolf of Wall Street and American Hustle.
But more important to the Hollywood studios, the MTV Movie Awards have become the ideal platform to promote their summer movies. This year's show promises exclusive footage from anticipated blockbusters like The Spider-Man 2 and X-Men: Days of Future Past. Some of the films' stars, including Andrew Garfield, Emma Stone, Jamie Foxx and Ellen Page, will introduce the clips.
The show was to also feature special honours to Mark Wahlberg and Channing Tatum, and a special tribute is planned for Paul Walker, who died in a car crash last November.