Poor households are more likely less resilient under climate change, risks of productive assets, social-related shocks, and decline of land productivity. The ability to deal with household resilience against poverty under the uncertain condition of risk is limited in the highlands of Ethiopia. The study aims to identify determinants of household resilience to livelihood insecurity under the crop-livestock mixed farming systems in Goncha district, Northwest highlands of Ethiopia. Primary data were collected by conducting face-to-face interviews among 280 households using structured questionnaire. Descriptive statistics, Kruskal-Wallis test and structural equation modeling were used to analyse the data. The results disclosed that sustainable management of the farming systems, cultivation of more fertile farmland, saving performance, diversification of income-earning activities, intensification of livestock husbandry practices, access to irrigation, and familiarity with practical technologies were found to be significant determinants at p<0.001 to household resilience of smallholder farmers. Social network development and tree plantation were explained household resilience to livelihood insecurity at P<0.01 and P<0.1 significant levels, respectively. The study concluded that scaling up sustainable management of the farming system and practical technologies, enhancing saving behavior, promoting income diversification, and intensifying agroforestry are significant for household resilience to livelihood insecurity of smallholders across agro-ecologies.