The COVID-19 pandemic is causing untold hardship across the world and Africa is not being spared. COVID-19 also tests the basic assumptions upon which the liberal international order is built, including the return to the primacy of national interests at the expense of advancing regional goods. Africa has followed Western prescripts of regional integration and constructed an elaborate edifice but remains excessively dependent on the global political economy for its survival and growth. There is a real danger that countries will draw back behind their borders in the belief that it will shield them from the fallout of COVID-19. Yet, the disruptive pandemic offers dynamic opportunities for Southern Africa and the continent to reclaim agency. To do this, we recommend that South Africa, as a prominent African and Global South voice, explores the regional and continental relevance of these seven opportunities. It should draw on its valuable experience of working with multiple partners at the levels of the AU and the UN. It should pursue these opportunities over the short- and medium-term with an inclusive set of regional partners: the SADC Troika and Secretariat, the region’s leading research institutions, civil society organisations, organised labour, the private sector, ICPs, and multilateral development agencies.