Adaptation to climate change is imperative for the resilience of smallholder agriculture in many developing countries. While studies have focused on climatic impacts on crops and adaptation decisions, barriers to the uptake of adaptation measures by smallholder farmers remain largely unexplored. We empirically quantified the adoption of adaptation measures, as well as barriers to adoption and their determinants for smallholder agriculture in Far Western Province, Nepal, based on a survey of 327 smallholder farmers. We established relationships between barriers and adoption for three different agroecosystems: the Mountain, Hill, and Terai. We then used multiple regression to identify the determinants of barriers in the broader study area, as well as across agroecosystems. We found that adaptation measures such as crop adjustment, farm management, and fertiliser management were practised across all regions. Techno-informational, economic, and environmental barriers were strongly and inversely correlated with adoption of adaptation measures. Adoption, barriers, and determinants varied across agroecosystems. The findings indicate that agricultural development policies must consider climate change adaptation measures tailored to specific agroecosystems in order to most effectively alleviate barriers and promote smallholder resilience.