<p>This study examines the relevance of governance quality in shaping the effect of economic policy uncertainty on several health expenditure indicators, including external health expenditure, national health expenditure, public health expenditure, and private health expenditure. The analysis is based on a sample of fifty-three African countries spanning 2005 to 2022. The adopted empirical strategy comprises the interactive dynamic two-step System Generalized Method of Moments (SGMM). The analysis is structured such that various governance dimensions—economic, political, and institutional governance moderate economic policy uncertainty to reduce health expenditure. Overall, governance dynamics do not effectively moderate economic policy uncertainty to negatively influence health expenditure dynamics. Specifically, a corresponding aggregated governance threshold of 2.2264, is needed to completely mitigate the positive effect of economic policy uncertainty on external health expenditure. Furthermore, improved infrastructure, employment, and foreign direct investment are potent channels for reducing some health expenditure dynamics within the continent. The associated policy implications of this study are discussed within the framework of the African Union’s Agenda 2063 and the United Nations Sustainable Development Goals (SDGs).</p>