<p>The majority of agricultural production in countries like Ethiopia depends on rainfall, and climate change primarily affects agricultural activities in such countries. However, different agro-ecological zones had varying degrees of susceptibility. Thus, the objective of this study was to investigate the agro-ecology based vulnerability of smallholder farmers in Gedeo and West Guji zones in Southern Ethiopia. The study measured the vulnerability elements in three agro-ecological zones using the LVI-IPCC vulnerability index. In this study, both primary and secondary data were used. For a household survey, 376 sampled households were randomly selected, and supplemented by focus group discussions and key informant interviews. The results revealed that different agro-ecologies have varying levels of vulnerability to climate change, with lowland agro-ecology being the most at risk due to its low adaptive capacity, high exposure, and sensitivity indices. Due to its higher adaptive capacity index, lower exposure index and moderate sensitivity index, the highland agro-ecology was the least susceptible with an overall vulnerability index of −0.26. Midland agro-ecology was deemed moderately vulnerable. The results highlighted that planned adaptation actions should take local conditions into account and that resilience building strategies are crucial for reducing the vulnerability of smallholder farmers. It is recommended to advocate for stronger policy measures to improve the community’s capacity for adaptation and reduce its exposure to climate change.</p>