Scott Waddington will be stepping down from his role as Brains chief executive after 17 years.
The move is part of a board succession planning process being undertaken by Brains' chairman John Rhys.
The search for his successor is expected to take around six months, during which time Waddington will remain in his post and oversee the family-owned company's move to its new brewery and head office facility in Cardiff Bay. The existing site in Cardiff city centre is being developed in partnership with Rightacres Property into a 2.5 million sq ft office, leisure and residential development.
During Waddington's tenure the company has grown its food business, acquired Coffee#1 in 2011 and rolled it out to an estate of 87 coffee shops, and continued to sponsor the Welsh Rugby Union and Football Association of Wales.
In the company's accounts filed for the year to 1 October 2016 the group reported a 7% increase in turnover to £135m, driven by Coffee#1 sales.
Waddington said: "With a number of our strategic priorities now reaching their conclusion, this felt like the natural time for me to move on to new challenges and to hand over to a new leader to take this great business on to its next stage of development."
Rhys added: "Scott has been a distinguished leader of the company over the past 17 years. I have enjoyed working with him during that time and look forward to doing so over the coming months whilst we search for the right person to lead the business into the next stage of our development."
Brains brewery was founded in 1882 in Cardiff and now controls more than 250 pubs and hotels in South Wales, Mid Wales and the West Country.