The coronavirus pandemic has had devastating effects on urban lives and livelihoods throughout the world. A major concern in the global North has been the hollowing out of central cities caused by remote working. The consequences for cities in the global South extend further and deeper because their economies are weaker, social and spatial inequalities larger, and healthcare systems more fragile. The paper explores the uneven trajectory of COVID-19 for people and places in South African cities, drawing on unique individual panel data. It shows how communities that were already the most vulnerable have been hit hardest by the pandemic, triggering hardship, hunger and social unrest. Local institutions will have to play a stronger role if society is to manage pandemics better in the future.