The electronic pioneers were among a second wave of acts including French DJ Laurent Garnier and Norwegian disco producer Todd Terje to be announced for the event.
Taking place from 5-7 September, Festival No.6 is held in the village of Portmeirion, Wales, home of cult TV series The Prisoner.
Other acts already announced for the event include Jon Hopkins, Don Letts, Greg Wilson and Peter Hook and The Light.
Bradley Thompson, festival director, said: ‘We are hugely excited to have such a truly iconic act as the Pet Shop Boys playing No.6 this year. They’re one of Britain’s biggest ever bands, but remain a brilliant, groundbreaking live act, and their headline slot is going to be incredible.
‘Together with other additions like Laurent Garnier and Todd Terje, this is without doubt our strongest line-up to date, and cements No.6’s position as the ultimate closing party to the festival season.’
Neneh Cherry with RocketNumberNine, Julion Bashmore, Andrew Weatherall, Danny Krivit and Steve Mason will also all be appearing at this year’s festival.
Please visit www.festivalnumber6.com for more information on the line up and tickets.