Event organiser Andy Copping confirmed the news over Twitter, announcing that the heavy metal act will play the main stage on the Saturday during the Donington Park weekender.
The Atlanta outfit join Motorhead, Slipknot, Iron Maiden and Queens of the Stone Age on the bill, with more bands to be confirmed in the near future.
Metallica, Black Sabbath and The Prodigy headlined this year's event
Mastodon are currently in the studio working on songs for the soundtrack to Pixar sequel Monsters University, which is due for release next summer.
Download Festival 2013 takes place from June 14 to 16 at Donington Park.
Watch the music video for Mastodon's 'Iron Tusk' below: