As South Africa and the rest of the world adjust to living with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), review and analysis of data on SARS-CoV-2 infections is needed to inform policy decisions for ongoing best outcomes. Drawing from South Africa's first national population-based household SARS-CoV-2 seroprevalence survey, this policy brief provides a comprehensive insight into the extent of the pandemic across age, sex, and localities between 2020 and 2021. It highlights lessons learned and recommends actions to continue responding proactively to the pandemic.