Julia Unwin, chief executive of the research and policy charity the Joseph Rowntree Foundation, is to stand down at the end of 2016 after 10 years in the role.
Unwin, who is also chief executive of the housing provider the Joseph Rowntree Housing Trust, will "pursue a number of new opportunities following her departure", a statement from the charities said.
This will include chairing a two-year inquiry into the future of civil society, funded by the Baring Foundation.
The JRF said recruitment for a successor to Unwin, who will also be expected to hold both roles, would begin over the summer, with the appointee expected to start in 2017.
Unwin, a former charity commissioner, said she had been "privileged and proud" to lead the organisations.
"At a time of great global, political and economic volatility, we have together worked to ensure that the needs and the aspirations of people and places in poverty are not overlooked, and that bold, practical and well-evidenced solutions are found," she said. "Nothing that has been achieved could have been done without the active engagement of trustees and staff, and I am grateful to all of them for the support and encouragement I have received."
Tony Stoller, chair of both charities, said Unwin had been an outstanding leader.
"She has overseen major changes in our research, policy, housing and care work, and has established herself as a foremost authority in all these fields, contributing to improved awareness and better policies across the four UK nations," he said.
"Her intellectual and practical contribution to our work to understand and overcome poverty in the UK has been second to none, and she has laid the groundwork for the future development of the JRF and the JRHT in the changing circumstances of the coming years."