He has been at the company, which owns TMW Unlimited, for 12 years and departs at the end of April.
Brien will not be replaced, and the Unlimited Group’s management team remains the same.
Creston sold to DBay Advisors in 2016 for £75.8m and then became a private company.
Brien said: "I am extremely proud of what we have achieved at Creston and with the Unlimited strategy we have built a marketing communications group leading the way in helping clients with the wide and varied challenges they are facing in this digital world.
"After the successful sale of the company at an attractive premium for shareholders and agreeing the next phase of the Group's journey, I believe now is the right time in my career to seek new challenges. I am confident my colleagues, along with DBay's support, will build on the success we have achieved to date."
Brien joined Creston in 2004 as chief operating and financial officer, and was promoted to group chief executive in 2014. He previously worked at Lowe Worldwide.
A statement from DBay said: "DBay has been a long term shareholder and enthusiastic supporter of Creston and we understand and respect Barrie's decision to leave for new challenges at this juncture in Creston’s journey.
"The management teams in our agencies will continue to innovate, create and deliver great results for all of their clients and the Board will continue to be chaired by our colleague Iain Ferguson."
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