To evaluate the level of food and key agricultural product supply security in Gansu Province, this study constructed a comprehensive evaluation index system based on five dimensions—supply quantity, quality, structure, economic security, and distribution security—and applied the entropy-weighted TOPSIS model to assess the 14 prefectures and cities in Gansu Province from 2018 to 2023. The results show that: (1) Under the “comprehensive food security” framework, the level of food security in Gansu Province has generally improved steadily, with the indices for all prefectures and cities showing an overall positive trend. (2) Geographically, there has been an overall improvement, but growth rates have varied across regions: the central and eastern parts of the Hexi Corridor and the Longdong region have seen strong growth, while growth in parts of the Longzhong and Longnan regions has been relatively slow. (3) From various perspectives, the quality and safety of supply are at the highest level; the economic security of supply exerts a strong driving force; the quantity security of supply is improving amid fluctuations, working together with distribution security to strengthen the system’s foundation; and the structural security of supply is being adjusted and optimized amid fluctuations. Based on this, while consolidating advantages in quality and growth drivers, efforts must be focused on addressing regional development imbalances to promote balanced development across the entire region.