There is growing concern about sustainable and equitable adaptation in climate change hotspots, commonly understood as locations that concentrate high climatic variability, societal vulnerability and negative impacts on livelihood systems. Emphasizing gender within these debates highlights how demographic, socioeconomic and agro-ecological contexts mediate the experiences and outcomes of climate change. Drawing on data from 25 qualitative case studies across three hotspots in Africa and Asia, analysed using qualitative comparative analysis, we show how and in what ways women’s agency, or the ability to make meaningful choices and strategic decisions, contributes to adaptation responses. We find that environmental stress is a key depressor of women’s agency even when household structures and social norms are supportive or legal entitlements are available. These findings have implications for the effective implementation of multilateral agreements such as the United Nations Framework Convention on Climate Change, the Sendai Framework on Disaster Risk Reduction and the Sustainable Development Goals.