This chapter show how throughout millennia, philanthropy has served as a catalyst for change and as a vehicle for community transformation. While COVID-19 has forced philanthropists worldwide to take immediate action and mobilise billions of dollars to save lives, African philanthropy and the culture of ‘giving’ are not new phenomena but are ingrained in the fabric of African societies. Before the arrival of colonialism, aid agencies and development partners, grassroots philanthropists and associations mobilised resources to address development issues. Within this context, the chapter focuses on the role of multi-sector partnerships in Africa and how they arose out of the crisis of the pandemic to drive the efficiency of vital collaborations between the African Union (AU), local governments, and the private sector. It shows how these partnerships helped the continent curb the pandemic and prevented the massive spread of infections. This chapter highlights the uniqueness and significance of these partnerships at the local and continental levels and identifies some of the core values underpinning them. The chapter also explores the importance and the impact of the AU’s strategic leadership and multi-sectoral partnerships in advancing the continent’s health and economic agenda while deconstructing some of the inherent challenges that were faced when trying to scale these alliances in Africa.