Alliance said Garrett-Cox, who became chief executive of its subsidiary Alliance Trust Investments (ATI) following a shake-up last October, would leave the company on March 11.
The group said it would reassign the responsibilities of the division's chief executive and ATI's investment team would continue to manage its £5bn of funds.
Operational responsibilities will pass to ATI's managing director Ramsay Urquhart.
In the restructuring last October, Alliance outlined plans to sell non-core investments, cut costs by £6mln this year and make the board fully independent, consisting wholly of non-executive directors.
It created separate boards for ATI and Alliance Trust Savings and said it may move to an external manager or managers rather than self-management in the future, but it would keep its existing investment team for now.
"This process is well underway and it is clear to us all that the role of chief executive of ATI has changed significantly. I and the rest of the board wish Katherine every success."
Shares in Alliance rose 7.8p to 464.5p in mid-morning London trading.