Central Asia features an arid and semi-arid climate, and the region is undergoing urbanization in the context of a fragile eco-environment. The influence of specific historical events in this region also persists on this ongoing urbanization. This study examines the mechanism of interaction between urbanization and the resource environment in Central Asia. The following results were obtained. (1) In different periods—Russian colonization, the era of the Soviet Union, and Central Asian countries as independent—the interactions between urbanization and the resource environment varied. (2) Variations in land use within 50 km of major cities of the region reflect both the trend of urbanization and that of variations in the eco-environment. In Kyrgyzstan and Tajikistan, where urbanization has been slow, the supportive effect of the eco-environment for urbanization was clear. In Uzbekistan and Turkmenistan, where freshwater resources are scarce, a close relationship was noted between urbanization and variations in the eco-environment. In Kazakhstan, fast urbanization has had a significant impact on the availability of water, grassland, and woodland in the relevant areas. (3) The efficiency of utilization of land and water resources is generally low. The compactness of the urban land of 47 major cities in Central Asia decreased from 0.44 in 1990 to 0.31 in 2015. Of them, 31 cities decreased in compactness, including all national capitals. Regardless of the level of urbanization, water consumption was high across the region. (4) The mechanisms of interaction between urbanization and the resource environment in Central Asia in the three stages were formulated to illustrate their specific temporal conductivity and spatial relevance.