Sustainable development of food security in Southwest China is critical in ensuring national food security, and concerns ecological civilization construction, ethnic unity, and poverty alleviation in China. A green- and ecological-oriented development approach is an important prerequisite for ensuring the sustainable development of food security in this region. In this paper, we first investigated the food production situation in this region, and then analyzed the challenges from the aspects of ecological environment features, agricultural inputs, and agricultural structure. Furthermore, according to the production conditions and resource endowment of Southwest China, we proposed a strategic vision comprising overall thinking, strategic positioning, general goal, and development path, as well as several policy suggestions focusing on policy modification and project implementation, aiming to provide references for the formulation of regional food security strategies.