The band will top the bill on the opening night of the three-day event at London's Hyde Park between July 13 and 15.
Soundgarden join Bruce Springsteen and Paul Simon as the headline acts for 2012, with Lady Antebellum, John Fogerty and Iggy & The Stooges all confirmed to play sets across the weekend.
Tickets for Soundgarden's Hard Rock Calling headline set will go on sale from 9am on March 30.
The group's performance at the festival will follow the UK leg of their 'Songbook' tour, which starts at Manchester's Lowry on June 16.
> Soundgarden's Chris Cornell denies rift with Kanye West
Listen to a clip of Soundgarden's new track 'Live to Rise' for the new Avengers movie below: