DJs Fearne Cotton and Greg James revealed that the 'Born This Way' singer will play the main stage on Sunday, May 15.
Other acts confirmed to perform at the event include the Foo Fighters, Black Eyed Peas, Jessie J and Nicole Scherzinger.
The two-day music event will take place on May 14 and May 15 at Carlisle Airport.
DJ Scott Mills earlier revealed that 40,000 tickets for the event will be allocated via a ballot. Anyone wishing to attend has to apply via the Radio 1 website, with registration opening tomorrow morning.
Last year's Big Weekend featured artists including Rihanna, Florence & The Machine, Cheryl Cole and Justin Bieber.
Watch the Lady GaGa 'Born This Way' music video below: