With the increasing recognition of climate change threats to agricultural productivity and food security, it is crucial to explore farming practices that increase productivity, adapt to the effects of global climate change, while lowering greenhouse gas emissions. This study investigates the factors that influence the adoption of climate-smart agricultural (CSA) practices among smallholder farmers in semi-arid Ghana, specifically, the Upper West Region (UWR) of Ghana. The study surveyed 400 smallholder farmers from eleven (11) Communities and employed stratified random sampling, and a logistic regression model for data analysis. The results revealed that knowledge of CSA benefits or motivation factors such as improved crop yields (OR=10.356; p < 0. 001), reduced input cost (OR=4.855; p < 0.05), influenced the decision of smallholder farmers to adopt CSA practices. Also, availability of support systems such as access to agricultural extension services (OR=10.358; p < 0.001) and CSA training (OR=4.374; p < 0.05) were significantly associated with the adoption of CSA practices. The findings also shows that demographic factors shape the adoption of CSA practices. Farmers within the ages of 26–45 were less likely to adopt CSA practices (OR = 0.050; p < 0. 05), while farmers with formal education were more likely to adopt CSA practices (OR = 9.262; p < 0.001) after controlling for support system variables. Based on the findings, improved crop yields, resilience, reduced input, support from Agricultural Extension Agents (AEAs), financial support, training, and government policies are factors that influence CSA adoption among smallholder farmers in the study area. The study calls for policymakers and non-governmental organizations (NGOs) to enhance financial support systems and extension services to farmers, as well as provide more training on CSA. Government policies should also be focused on education and sensitization to upscale the adoption of CSA practices for its maximum benefits.