Despite a half-century-long global eradication effort, polio continues to have a devastating impact on individuals and communities worldwide, especially in low-income countries affected by conflict or geographic barriers to immunization programs. In response, the World Health Organization (WHO) Global Polio Eradication Initiative (GPEI) employs disease surveillance and vaccination campaigns coordinated through the WHO Regional Office for Africa (AFRO) Geographic Information System (GIS) Centre. Established in 2017, the AFRO GIS Centre played a key role in the eradication of wild-type polioviruses (WPVs) in 2020, but the COVID-19 pandemic, emergence of circulating vaccine-derived polioviruses, and transmission of WPV1 from Central Asia have led to a resurgence of polio in Sub-Saharan Africa. The AFRO GIS comprises a set of mobile device or cloud-based tools for geospatial data collection, analysis, and visualization. Using tools such as Auto-Visual Acute Flaccid Paralysis Detection and Reporting, electronic surveillance, and Integrated Supportive Supervision, GIS personnel collect polio case numbers and locations, track field worker activities, follow the movements of nomadic populations vulnerable to polio and other diseases, and determine needs for further healthcare deployments. The system is location specific and operates in real time, enabling the AFRO GIS to promptly target its responses to polio, COVID-19, Ebola virus disease, and other public health crises and natural disasters. The present review describes the components of the AFRO GIS and how the AFRO GIS Centre coordinated on-the-ground polio eradication efforts to help secure Africa’s certification as WPV free. It also examines current and prospective challenges regarding other disease outbreaks in the COVID-19 era and how the AFRO GIS Centre is addressing these ongoing public health needs.