Initial policy responses implemented by African governments, following the onset of the COVID-19 pandemic, are assessed, including lockdowns, restrictions of international travel, and other stringency measures (such as social distancing and contact tracing) to contain the spread of the COVID-19 pandemic from March 2020 to November 2020. Policy lessons on potential trade-offs between the economic and social consequences and the effort to save lives are drawn. We used novel data to establish causal relationships between infection rates of SARS-CoV-2 and stringency measures implemented by governments, as well as their economic and social consequences. The Instrumental Variable (IV) Method was used to identify the direction of causation. Our estimates showed that compliance with mobility restrictions led to a significant decline in infection rates, with the impact amplified in situations in which complementary measures were strong. The economic and social consequences were also very substantial, including contractions in real gross domestic product (GDP) and deterioration of household welfare. There were also a high incidence of lockdown-related violence and criminal activities. The lockdowns to fight COVID-19 could be most effective in the contexts of a strong health care system, efficient infectious disease control infrastructure, and community understanding. In other contexts, the trade-off between saving lives and preserving livelihoods could be very costly, and in extreme cases, lead to unintended consequences, such as severe hunger, violence, and permanent loss of jobs.