ABSTRACT African First Ladies are categorised into two: the less powerful First Ladies, the behind-the-scene actors, making positive contributions to their spouses’ regime and the powerful First Ladies whose arbitrary powers and overarching presence pose real threat to the regime. Extant studies concentrate on the former and pay scant attention to the latter. Drawing on the activities of Patience Goodluck Jonathan, Nigeria’s former First Lady, this paper explores the ways Patience and other powerful African First Ladies contribute to regime change in emerging African democracies. In doing so, the paper explores the anatomy of female power and its intricate interface with the Office of the First Lady, the framework for appropriating and exercising the power of the First Lady. The goal is to provide the theoretical basis for understanding the empirical, that is, the practical ways Patience Jonathan and other powerful First Ladies appropriate power and contribute to regime change in Africa.