Ethiopia is one of the world’s most vulnerable countries experiencing drought and floods as a result of climate variability and change. This study examined the major climatic changes experienced by farm households in the lowlands of Southern Ethiopia. It utilized a mixed methods sequential explanatory design approach to triangulate quantitative data with qualitative data. Using a multi-stage sampling procedure, 400 farm household heads participated. Moreover, meteorological data were acquired from the National Meteorology Agency for the period from 2000 to 2019. Descriptive statistics, rainfall anomalies, and coefficient variation were used for data analysis. The findings show that over the last 20 years, the frequency and intensity of extreme weather had increased, and there was an overall change in the seasonality of rainfall. Drought assessment results showed that 2004, 2009, 2012, 2015, and 2017 were all drought years in the study districts. The results revealed that reduced crop production, flooding, crop losses, drought, malaria, and animal disease were the major climate change impacts that farm households experienced in the lowlands of Southern Ethiopia. The study suggests that drought-resistant crops and water harvesting schemes should be promoted to minimize the effects of climate change.