The article examines the historically significant period of N.I. Vavilov’s activities and his team in conducting 108 expeditions and collecting plant seeds in more than 1000 countries worldwide. By 1940, the collection was the largest in the world. Vavilov’s research aimed to study the genetic potential of seeds, establish centers of origin for wild and cultivated plants, their role in human practical activities, and the formation and replenishment of the collection initiated before the revolution by the founders of applied botany. Additionally, the article analyzes the challenging periods experienced by the collection, such as the formation of Soviet Russia, the Siege of Leningrad, and participation in the restoration of the devastated agriculture after Victory in World War II. Special attention is paid to the involvement of employees of the Federal Research Center “N.I. Vavilov All-Russian Institute of Plant Genetic Resources” (VIR) in preserving the collection during the Siege of Leningrad. The practical application of the research results lies in understanding the importance of preserving plant genetic resources for food security and sustainable development of rural regions. The publication emphasizes not only the historical value of the seed collection but also its contemporary significance as an important resource for scientific research and practical use in agriculture. The scientific article also highlights the heroic efforts of VIR employees, who endured the harsh conditions of the Siege of Leningrad but continued to carefully preserve plant seeds, contributing to the survival and revival of agriculture in our homeland. The dedication and professionalism of the employees to the cause are underscored. Thus, the article reveals the historical and practical significance of the VIR seed collection, an important national genetic resource that continues to serve the goals of agricultural science and practice.