Oxfam chief executive Mark Goldring is to stand down following the scandal involving claims of sexual misconduct by staff in Haiti, the charity says.
Mr Goldring, who was criticised for his handling of the claims that aid workers used prostitutes in 2011, said someone else should "rebuild" the charity.
He has held the position since 2013 and will leave at the end of the year.
In a statement Mr Goldring said: "This journey will best be led by someone bringing fresh vision and energy."
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The British charity was accused of concealing the findings of an inquiry into claims staff sexually exploited female victims of the 2010 earthquake in Haiti.
An Oxfam spokeswoman said his resignation was "absolutely not to do with his handling" of the crisis.
Oxfam chairwoman Caroline Thomson said it was with "great sadness" she accepted his resignation, adding that he "faced the test of a lifetime managing the crisis which hit us in February and related to events before he joined".
Mr Goldring appeared in front of MPs that month, apologising for the actions of staff and also for his own comment to the Guardian that the charity was being attacked as if it had "murdered babies in their cots".
He denied there had been a cover-up and also said he would not step down unless the charity's board lost faith in his leadership.
Oxfam's deputy chief executive, Penny Lawrence, resigned in February over the handling of the claims.
The allegations, reported in The Times, said Oxfam's country director for Haiti, Roland van Hauwermeiren, used the services of prostitutes at a villa rented for him by Oxfam in the aftermath of the 2010 earthquake.
According to the paper, Oxfam knew about concerns over the conduct of Mr van Hauwermeiren and another man when they worked in Chad before they were given senior roles in Haiti.
The charity's own investigation in 2011 led to four people being sacked and three others resigning, including Mr van Hauwermeiren.
It produced a public report, which said "serious misconduct" had taken place in Haiti - but did not give details of the allegations.
In announcing his resignation, Mr Goldring said: "Following the very public exposure of Oxfam's past failings, we have redoubled our efforts to ensure that Oxfam is a safe and respectful place for all who have contact with us.
"We are now laying strong foundations for recovery. I am personally totally committed to seeing this phase through.
"However, what is important in 2019 and beyond is that Oxfam rebuilds and renews in a way that is most relevant for the future and so continues to help as many people as possible around the world build better lives."
He will continue to lead the charity until a successor is found.