To overcome the challenges of climate change, this study was intended to identify factors that affect the farmers’ adoption of CSA in the Ilu Aba Bora Zone of Southwest Ethiopia across varying agro-ecological zones. A mixed research design was used for this study. During this study, representative districts (Bure, Hurumu, and Nono Sale) were selected purposely based on their differences in agro-ecology, while rural kebeles and respondents were selected randomly from the districts to minimize the biases of the data. Data collection tools employed were a questionnaire, KKI, FGD, and field observations. A binomial logistic regression model was used to identify the interaction of response and explanatory variables and to draw a conclusion. The findings of this study revealed the majority (63.1%) of farmers did not have an understanding of the meaning, function, and goals of CSA practices. Existing CSA options in the study area were conservation agriculture, crop diversification, agro-forestry, early warning system, livelihood diversification, and improved livestock feed, which were practiced at different levels and by a few households. In particular, the early warning system and improved livestock feed were the least implemented CSA options, whereas livelihood diversification, conservation agriculture, and agro-forestry were the highly adopted practices in the area. Independent variables including on-farm income, farming experience, weather information, agro-ecology, farm land size, age, extension service, marital status, and off-farm income were the factors significantly affecting the adoption of CSA practices in the study area. Experts, governments, and nongovernmental organizations should improve farmers’ awareness of the benefits of CSA practices in ensuring food security, climate mitigation and adaptation through training and capacity building. The result of this study will show the direction for farmers, policy makers, planners, and other stakeholders to set up a solution in order to promote CSA practices and technologies based on agro-ecology.