Andrew Hore is to leave his role as Ospreys chief executive to take over at Australian Super Rugby side Waratahs in April.
Former Ospreys prop Andrew Millward will become their managing director.
Hore, 43, a former Welsh Rugby Union and New Zealand Rugby high performance manager, has been chief executive of the Pro12 outfit since 2013.
He previously confirmed the Waratahs' interest in him on the day Ospreys announced a first profit since 2007.
Hore, who became Ospreys elite performance boss in 2008, has also been named as the new chief executive of the New South Wales Rugby Union (NSWRU) in Australia.
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Waratahs' chief executive Greg Harris has left after a restructure involving them and the NSWRU.
"As a seasoned administrator, with experience in international rugby circles, Andrew brings to the joint CEO role a unique set of competency skills that distinguished him from the other quality candidates in the global search," said Waratahs chairman Roger Davis.
Hore came to Wales as conditioning coach under then-national coach Steve Hansen in 2002, left in 2005 to join New Zealand Rugby Union as high performance manager and three years later arrived at Ospreys.
He went on to hold the title of chief operations officer at Ospreys in 2010 and chief executive in 2013.
Ospreys chairman Roger Blyth said: "Andrew brought energy, drive and knowledge to the Ospreys during his time here and I'm sure Andrew would agree he has also learnt considerably from our environment, allowing him to develop as a manager."
'Ospreys don't get full credit within Wales'
Hore says his decision to leave was "difficult" and comes after an "incredibly difficult period for both the Ospreys and the wider game in Wales".
He added: "We've come through that period thanks to a huge collective effort from so many people and, I believe, Ospreys Rugby as a business is in a far better position than could have been hoped just a few years ago.
"I genuinely believe that the Ospreys don't get full credit within Wales for what they have achieved over the years, be that commercially with the business now a profitable and sustainable one, or, continuously, in rugby terms, where they lead the way by any measurement possible.
"I hope that will change in the years to come, particularly in what is a rapidly evolving rugby, media and business landscape in Wales."
Ospreys chairman Roger Blyth said: "Everyone at the Ospreys will be well aware of the impact Andrew has had across all areas of the business during his time here, and will be forever grateful for all his efforts to improve our organisation."
Millward moves up from the role of rugby general manager, having previously been regional performance manager.
"It's an exciting opportunity for me and I'm looking forward to continuing to play a part in ensuring we stay at the forefront of European rugby, on and off the field," Millward told the Welsh region's website.
Former Swansea and Wales full-back Blyth said: "Andrew (Millward) will take on most of the current CEO's duties while, where necessary, we will look at other areas within the business to fully cover the role. "
Blyth added: "With Andrew (Millward) stepping up to the new role, it provides an opportunity for us to enhance the senior rugby management team and strengthen our day-to-day operations at Llandarcy and that is something we are presently looking at."