The intersection of climate change, environmental degradation, and health presents urgent and complex challenges for Africa’s most vulnerable populations. Although the continent contributes less than 4% to global greenhouse gas emissions, it faces a disproportionate burden of climate-related health impacts due to ecological fragility, socio-economic inequalities, and under-resourced health systems. This chapter explores how climate-induced stressors—ranging from rising temperatures and erratic rainfall to coastal erosion, vector expansion, and disease outbreaks—exacerbate existing health vulnerabilities across diverse African settings. Drawing on empirical examples from across the continent, the analysis highlights both direct and indirect health outcomes, including heat stress, respiratory and waterborne illnesses, food insecurity, mental health strain, and displacement. Special attention is given to demographic and occupational groups such as women, children, the elderly, persons with disabilities, and informal workers, who experience heightened exposure and reduced adaptive capacity. The chapter also critically examines policy responses, governance frameworks, and the role of community-based and ecosystem-based adaptation strategies in fostering health resilience. Gaps in data, institutional coordination, and investment are identified as persistent barriers. Through an integrated lens, the chapter calls for transformative, equity-driven approaches that prioritize localized solutions, participatory governance, and the mainstreaming of climate-health linkages in national and regional planning.