Ms Mainland is to take up a new job as the executive director of the Melbourne Festival in Australia in February.
She said she was "immensely proud" of the Fringe society staff and their achievements.
The Edinburgh Fringe is the world's largest and best known open-access arts festival.
This year's Fringe had an estimated 2,298,090 tickets issued for shows across Scotland's capital.
Chairman of the Edinburgh Festival Fringe Society, Sir Timothy O'Shea, said: "Her enthusiasm is contagious, her spirit is generous, and her vision and hard work has been truly remarkable. We are extremely sad to see her go."
Ms Mainland, originally from Orkney, joined the Fringe society in 1991 as an administrative assistant.
In 2005, she became general manager of the Edinburgh International Book Festival and was administrative director there until 2009 when she took up the newly-created post of chief executive of the Edinburgh Festival Fringe Society.
She took over the Fringe the year after her predecessor resigned in the wake of a box office fiasco that led to a 10% slump in ticket sales.
In June last year she received a CBE in the Queen's Birthday Honours list.
The chief executive of the Edinburgh Fringe, Kath Mainland, has announced she is stepping down after almost seven years in the role.