Monitoring and evaluation (M&E) is an essential component of public health emergency response. In the WHO African region (WHO AFRO), over 100 events are detected and responded to annually. Here we discuss the development of the M&E for COVID-19 that established a set of regional and country indicators for tracking the COVID-19 pandemic and response measures. An interdisciplinary task force used the 11 pillars of strategic preparedness and response to define a set of inputs, outputs, outcomes and impact indicators that were used to closely monitor and evaluate progress in the evolving COVID-19 response, with each pillar tailored to specific country needs. M&E data was submitted electronically and informed country profiles, detailed epidemiological reports, and situation reports. Further, 10 selected key performance indicators (KPIs) were tracked to monitor country progress through a bi-weekly progress scoring tool used to identify priority countries in need of additional support from WHO AFRO. Investment in M&E of health emergencies should be an integral part of efforts to strengthen national, regional and global capacities for early detection and response to threats to public health security. The development of an adaptable M&E framework for health emergencies must draw from the lessons learned throughout the COVID-19 response.