Calcraft said he had spent the past two years "handing over my responsibilities to ensure that the family will continue to go from strength to strength… I will always love Mother".
But he admitted that "new collaborations, alliances and ventures hold great appeal", adding: "The opportunities to create positive change are more profound than ever before."
Calcraft sold his 25 per cent stake back to the agency in 2012 for £6 million and resigned from the board. At the time, he said it was "business as usual".
Robert Saville, who founded Mother with Calcraft, Mark Waites and Libby Brockhoff in 1996, said: "There are few people who you come across in your life that you can say make a significant impact. Stef is one of those. "He is a force of nature and Mother wouldn’t have been the same without him."
Since 1996, Mother has expanded through new offices including in New York and Buenos Aires, as well as joint ventures such as the communications planning agency Naked Communications and the digital shop Poke. Photon (now Enero) bought Naked in 2008 and Publicis Groupe acquired Poke last year.
Calcraft said: "It has been my privilege to share the Mother table with some of the most talented creative entrepreneurs on the planet. Special mention must also go to the most extraordinary group of clients who came looking for something better and have become partners in a global success story."
Before founding Mother, Calcraft worked at Bartle Bogle Hegarty and Leo Burnett. He began his career on the client side at Unilever.