Livelihood resilience is the ability of individuals, families or communities to withstand external shocks based on existing resources. It is an important research paradigm in sustainable development studies. The outbreak of COVID-19 and strict epidemic prevention policies have greatly impacted the production and life of rural farmers in China. The resilience of farmers’ livelihoods during the epidemic is crucial to the sustainable development of their livelihoods and regional stability. This study uses classic buffer capacity, self-organization ability, and the capacity for learning a three-dimension livelihood resilience framework using the comprehensive index, OLS, and geographical detector methods based on Hubei province and neighboring Anhui and Chongqing. Rural household survey data investigate the background of epidemic hit the livelihood of farmers resilience and its spatial distribution pattern and identify the key influencing factors. The results show that the livelihood shock faced by farmers was higher than the risk of disease, and the overall level of livelihood resilience was low after the pandemic. Financial capital and social capital can effectively help farmers to eliminate livelihood difficulties. In contrast, natural capital has a limited driving force, and physical and human capital have no obvious impact. The spatial agglomeration differentiation is obvious, indicating that the impact of COVID-19 on livelihoods was closely related to the degree of local socio-economic development and geographical location. The results of this study provide targeted recommendations for the development of epidemic prevention and livelihood resilience policies tailored to local conditions, emphasizing the importance of boosting livelihood recovery at both the government and household levels.