<p>This study investigated the effects of resource rent and infrastructural development on entrepreneurship in Africa and how governance institutions on the continent are moderating these relationships. The dynamic system GMM estimation approach and a panel of 34 African economies were used over the period 2010–2021. The analysis uncovered several important findings. First, we found that while infrastructural development significantly promotes entrepreneurship in Africa, resource rent significantly hampers it. Second, we found that instead of reducing the adverse effect of resource rent on entrepreneurship in Africa, governance institutions on the continent are intensifying it. However, we did not find evidence that governance institutions in the region are adversely influencing the infrastructure-entrepreneurship relationship. Third, we also established that foreign direct investment inflow is an important driver of entrepreneurship in Africa, while economic policy uncertainty is a deterring factor. Consequently, the study underscored the importance of prioritizing institutional reforms to ensure reduced uncertainty in the policy environment, enhanced transparent resource management, increased infrastructural investment, and sustainable entrepreneurship development in Africa.</p>