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The powerhouse line-up includes Kiwi soul sensation Teeks, indie-pop star Gin Wigmore and Dunedin’s own Nadia Reid and Her Band.
Lord Echo’s Percussion People, Frank Booker, Peter Urlich, Kedu Carlo, Juno Is and Hurricane Emily will also perform throughout the day/night event, across multiple stages at the University of Otago Oval.
Festival organiser Jason Schroeder said the entertainment would get even better when another headline act and second line-up was announced in January.
Up to 5000 people are expected to attend the R18 event, which will run between 3pm and 11pm on April 2.
Mr Schroeder said it was an exciting time for Dunedin, particularly because there had been few, if any, major events in the city for more than a year.
"We are absolutely stoked to be bringing an amazing line-up of iconic Kiwi musicians to Dunedin.
"We know the city and the wider region have been aching for a new large-scale event and we’re ready to make it happen."
Fortune Festival is the result of international event promoters Live Nation and local event promoter Common People Entertainment joining forces with Dunedin Venues Management Ltd (DVML).
Live Nation promoter Mike Ross said Kiwi musicians were quick to join the festival.
"Like us, our musicians see the potential for an amazing new event in Dunedin that will provide the South entertainment and a large number of visitors who will travel to an event of this calibre."
DVML chief executive Terry Davies said the event had come together "amazingly", and he believed the line-up of acts would bring new energy to the city.
Pre-sale tickets go on sale on Monday and public sales will open next Thursday.