The band will top the bill on the festival's main stage when it returns to Castellón between July 18-21.
They join previously confirmed acts The Killers and Queens Of The Stone Age in the lineup, while Jake Bugg, Azealia Banks and Palma Violets will also play sets.
Arctic Monkeys are expected to tour the festival circuit this year in support of their upcoming fifth studio album, which serves as the follow-up to 2011's Suck It And See.
Tickets for Benicassim 2013 are on sale now, with weekend tickets currently available for the special price of £145. VIP tickets are also on sale for £325.
Watch the music video for Arctic Monkeys' 'R U Mine?' below: