Cynthia Carroll will step down from her role as Anglo American's chief executive after six years at the helm.
Her exit leaves just two female bosses in the FTSE 100.
Australian Mark Cutifani has now been appointed CEO. He will take up the reins in April and will aim to reverse the company's fortunes, which witnessed a $14bn (£8.7bn) fall in market value over the past five years. He joins from AngloGold - a spin-off company from Anglo American.
The departure of Carroll - an American - and the first woman and non-South African to head up the global mining giant, follows in the wake of Dame Marjorie Scardino's exodus from publisher Pearson.It will be seen as something of an embarrassment for the government as it tries to drive up female representation in the boardroom.
Carroll had long faced a growing wave of shareholder pressure following a series of wildcat strikes at its South African mines and accusations of 'poor decision making' from one of Anglo's biggest investor's, South Africa's Public Investment Corporation.
When news of her departure was first announced in October 2012, shares in the company rose 4%.
Carrol argued against the 'tokenism' of female CEO's stressing the need for companies to 'develop' women so that they are 'capable of delivering and doing the job effectively'.
The latest Cranfield School of Management report (March 2012) into female executives showed an increase in the number of female-held directorships after a three-year plateau.
Released a year after the publication of the Davies report - which recommended at least 25% of board roles in FTSE 100 companies by 2015 should be held by women - the findings saw current figures at 15.6%.
This was a rise on the 12% that had remained unchanged for the previous three years, while the number of companies with no woman on the board dropped to eleven and businesses with more than one woman on the board increased to 50.
The report also found that of the 47 new female appointments, 29 had had no previous FTSE board experience, suggesting the process of appointing board members was opening up.
Should that trend continue, the report predicts the minimum recommendations set by the Davies report, will be achieved with 26.7% of directors being female by 2015, and 36.9% five years further down the line.
Fiona Hotston Moore, a partner at accountancy firm Reeves and an active campaigner to put more women in boardrooms, said Carroll's departure was 'disappointing'.
She said: 'There was a lot of fanfare to say that things were changing and moving in the right direction, but a lot of that change is in NED positions where it is more about changing the colour of the flowers than strategy. The reality is that the number of female executives in strategic roles is going down.
'What would be great is if male chairmen got involved in actively growing and mentoring women rising through the ranks. So far we haven't seen that. We need the endorsement of more chairmen to make that change.
'We also need to see a real change in the attitude of search agencies who at the moment, are not helping to change the attitude of chairmen.'
Carroll received £2m in salary and bonuses in 2011, in addition to £445,000 payment from a share-based bonus plans that came to fruition during the year.