Climate change is likely to have wide-ranging impacts on maternal and neonatal health in Africa. Populations in low-resource settings already experience adverse impacts from weather extremes, a high burden of disease from environmental exposures, and limited access to high-quality clinical care. Climate change is already increasing local temperatures. Neonates are at high risk of heat stress and dehydration due to their unique metabolism, physiology, growth, and developmental characteristics. Infants in low-income settings may have little protection against extreme heat due to housing design and limited access to affordable space cooling. Climate change may increase risks to neonatal health from weather disasters, decreasing food security, and facilitating infectious disease transmission. Effective interventions to reduce risks from the heat include health education on heat risks for mothers, caregivers, and clinicians; nature-based solutions to reduce urban heat islands; space cooling in health facilities; and equitable improvements in housing quality and food systems. Reductions in greenhouse gas emissions are essential to reduce the long-term impacts of climate change that will further undermine global health strategies to reduce neonatal mortality.