Miller has been replaced by David Alexander, former international director of British Red Cross, who will be Merlin’s interim chief executive during a transition phase expected to last about 18 months.
Merlin has said it will remain a separate legal entity for the time being and that this will be reviewed during the transition.
The charity said in its announcement that both Miller and Save the Children "felt it was appropriate that a new CEO was appointed to lead the organisation through a period of change and growth".
Asked about the terms of her departure and her future plans, a spokeswoman for Save the Children referred Third Sector to a press notice on Merlin’s website that does not address these questions.
Miller had led Merlin since 2005, shortly after the Asian tsunami prompted its largest-ever emergency response, and was this year awarded a CBE for her humanitarian work.
The charity now has an annual income of £55m, as well as 3,700 staff across the world.
"I have loved leading Merlin and would like to sincerely thank not only the thousands of dedicated staff working in some of the most difficult areas of the world, but also the public who have supported Merlin in so many ways," Miller said in a statement. "I am looking forward to watching Merlin and Save the Children continue to save lives in some of the world’s toughest places."
Lord Michael Jay, the former chair of Merlin, paid tribute to Miller’s stint as chief executive, saying the charity was "immensely grateful for her leadership."