The problem of food insecurity has become increasingly critical across the world since 2015, which threatens the lives and livelihoods of people around the world and has historically been a challenge confined primarily to developing countries, to which the countries of Central Asia, as typical transition countries, cannot be immune either. Under this context, many countries including Central Asian countries have recognized the importance of trade openness to ensure adequate levels of food security and are increasingly reliant on international trade for food security. Using the 2001–2018 panel data of Central Asian countries, based on food security’s four pillars (including availability, access, stability, and utilization), this study empirically estimates the impact of trade openness and other factors on food security and traces a U-shaped (or inverted U-shaped) relationship between trade openness and food security by adopting a panel data fixed effect model as the baseline model, and then conducts the robustness test by using the least-squares (LS) procedure for the pooled data and a dynamic panel data (DPD) analysis with the generalized method of moments (GMM) approach, simultaneously. The results show that: (1) a U-shaped relationship between trade openness and the four pillars of food security was found, which means that beyond a certain threshold of trade openness, food security status tends to improve in Central Asian countries; (2) gross domestic product (GDP) per capita, GDP growth, and agricultural productivity have contributed to the improvement of food security. Employment in agriculture, arable land, freshwater withdrawals in agriculture, population growth, natural disasters, and inflation rate have negative impacts on food security; and (3) this study confirms that trade policy reforms can finally be conducive to improving food security in Central Asian countries. However, considering the effects of other factors, potential negative effects of trade openness, and vulnerability of global food trade network, ensuring reasonable levels of food self-sufficiency is still very important for Central Asian countries to achieve food security. Our research findings can provide scientific support for sustainable food system strategies in Central Asian countries.