Rich ancient societies of central Asia developed on the basis of trade between East and West; their existence was dependent on natural resources that favoured agriculture. The branches of the Silk Road in central Asia clearly coincide with loess areas, where many settlements were erected based on the presence of fertile loess soil and water. The aim of the study was to analyse the environmental factors that led to the growth and decline of one of the most important Silk Road “loess towns,” ancient Panjikent, as an example of human and climatic impacts on landscape changes. The town, established in the fifth century, quickly became one of the most important cities of Sogdiana. Local loess material was used for the production of the sun-dried bricks. Rapid population growth led to deforestation and consequently increased the intensity of erosion rates and reductions in cultivation area. A period of drought near the end of the first millennium AD influenced the final abandonment of the ancient town and its relocation to the lower terrace of the Zarafshan River. A decline in natural and agricultural resources and subsequently climatic forces caused a decline in the number of cities in semiarid regions of central Asia.