Staff at the agency were told today that Creighton will be leaving at the end of July. There are currently no plans to replace him.
Creighton said he will be taking a break "and then determining what the next exciting new chapter will be for me".
Creighton joined DAN in 2015 from Mindshare UK where he was chief executive.
His departure comes after a string of changes at the business including Jo Sutherland taking over at Carat from Rick Hirst.
Stef Calcraft, executive chairman of Dentsu Aegis Network UK & Ireland, said: "Mark has been a key member of the leadership team over the past two and a half years and I greatly appreciate his support since I joined the business at the start of this year. He is taking a well-earned break to pursue some of his broader interests before he decides the next step in his career. I’d like to thank Mark for his valuable contribution to the business and wish him every success in the future."