Jo Sutherland, chief executive of Carat UK, is leaving the business at the end of the year.
Agency staff were told today in an internal memo.
Sutherland has been CEO of Carat (Dentsu's biggest media shop) since 2018 when she took over from Rick Hirst. However she has worked at parent company Dentsu for more than 20 years.
Before joining Carat she was managing director across EMEA for mobile agency Fetch (now part of Dentsu X). She has also worked at Vizeum.
During her time as CEO of Carat, Sutherland has helped the agency win clients including Mondelez, Co-Op, Vodafone, Pandora, Beiersdorf, Legal & General, Lionsgate and Kraft Heinz.
She said: "After more than 20 years working at the business in various guises, I have decided that now is the right moment for me to step down and to start a new adventure. It's been a huge privilege and immense source of pride to have led Carat over the last three years.
"I'm delighted to be leaving Carat in such good shape and with such a strong leadership team in place. It's been a pleasure to work with the team there and I shall look forward to watching them continue to thrive."
Carat has yet to announce a replacement. In the meantime Hamish Nicklin, executive director for media at Dentsu, will work with the Carat leadership team to "ensure a smooth transition of responsibilities".
He said: "Throughout her time with the business, Jo has consistently demonstrated her ability to truly understand the challenges that client's face and identify how they can utilise media to solve them.
"This is coupled with a real awareness of how to embed and maintain a strong agency culture, which together have seen her succeed across all the different roles that she has held with our business.
"Personally, I am sad to see her go and would like to thank her for contribution during her time with the business. On behalf of everyone in the organisation, we wish every success in the next stage of her career"
Campaign reported last week that the international arm of Dentsu is planning to cut around 6,000 jobs. Sutherland's departure is not understood to be part of this.