Save the Children chair Alan Parker resigned on Thursday, citing a "complex mix of challenges" as the reason for his early departure.
The Brunswick Group chair's decision to step down from the global organisation cuts short his 10-year term, which was due to end in December.
"Given the complex mix of challenges the organisation and the sector is facing, it is my view that a change is needed," Parker said in a statement.
He did not detail a specific reason for his resignation, although noted "some unacceptable workplace behaviour" at the charity's London headquarters during his tenure.
Parker referred to cases between 2012 and 2015 involving Brendan Cox, widow of murdered British MP Jo Cox, and the charity's former chief executive Justin Forsyth.
Both cases were dealt with through internal procedures with external legal support.
"These issues are now subject to further review by the Charity Commission. This is an important review and I will work with them to assist in any way I can," Parker said.
A leaked 2015 report from Save the Children suggested that Parker's "very close" relationship with Forsyth may have affected how he responded to complaints.
The charity sector was embroiled in a sexual misconduct scandal in February after allegations were intially raised involving prostitution in Haiti by Oxfam aid workers.
Kevin Watkins, chief executive of Save the Children UK, said at the time that the charity dealt with 193 cases of "child safeguarding" issues in 2016.
Following those complaints there were 53 full investigations, 20 case referrals to police and 11 staff dismissals, Watkins told a British parliamentary committee.