Carole Easton is to leave the Young Women’s Trust at the end of May after more than six years as chief executive.
Easton led the trust, which is more than 150 years old, through its second major rebrand this decade.
"Despite the undoubted progress we have made, there is so much more for the trust to do and sadly its work is needed more than ever," she added.
The charity transferred 64 staff to Changing Lives at the end of 2013 after concluding that its structure was unsustainable.
A spokesman for the trust, which supports young women, said Easton planned to look at consultancy and interim roles.
"It was very much her decision to leave," the spokesman said. "She felt it was time for a new challenge."
The trust began advertising yesterday for a new chief executive.
The spokesman said it hoped to conduct interviews in April and the senior management team would "cover any gaps" if a successor was not ready to start by the time of Easton's departure.
Jo-ann Robertson, chair of the trust, said Easton's "dedication and unwavering commitment" had enabled the charity to go from strength to strength.
The trust's annual report for the year to the end of March 2018 said it generated income of £1.1m and spent £3.2m.
The report attributed the scale of the deficit to the decision to withdraw from a multi-employer, defined-benefit pension scheme with the Pensions Trust, a workplace pensions provider, which it said had a "major impact on the financial results".
It said the full costs of withdrawal were £3.5m, of which £1.5m was included in the 2017/18 accounts.