The annual free music festival was previously staged there in 2004, and will return as it marks being named UK City of Culture for 2013.
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The event has been expanded to three days for the first time, and will be held from May 24 to May 26.
The first day of the weekend will focus on dance music and Radio 1Xtra, and will be located in the city centre with two main stages.
Nick Grimshaw announced the location and first acts during his Radio 1 breakfast show today (Thursday, January 31), which is broadcasting live from Derry.
Headline acts and the full lineup will be announced over the coming months.
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Young people of Derry will be invited to take part in Radio 1 and 1Xtra's academy for a series of workshops running from May 13 to May 17.
Jason Carter, BBC Head of Live Music and Events, Popular Music, said: "The last Big Weekend in the city in 2004 was a legendary music moment in Northern Ireland, and it's so great to be able to return with an even bigger show second time around."
Ticket details will also be announced soon.
Last year's Radio 1 Hackney Weekend took place in east London to celebrate the Olympic Park, with Jay-Z and Rihanna headlining.
Radio 1 Hackney Weekend 2012 - photo gallery: