Henrietta Fore, 69, will replace Anthony Lake who has served as executive director of the UN Children's Fund since 2010.
In announcing the appointment by Secretary-General Antonio Guterres, a UN spokesman said Fore had worked in US public service, the private sector and for non-profit organisations over the past four decades.
She was the first woman to head the US Agency for International Development (USAID) and served as director for foreign assistance in the US State Department.
Guterres has pledged to appoint more women to senior positions at the United Nations. Only about a quarter of the UN's senior leadership posts are held by women.
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