Sustainability has always been an emphasized topic in policy making and planning in the agricultural sector of developing countries. Despite this fact, sustainable agriculture has not been realized so far because of the various complex challenges in these countries. The lack of a structured scientific research on these challenges prompted us to conduct a study to fill this research gap and to create useful knowledge on this issue. In this regard, 300 Iranian agricultural experts, selected through stratified random sampling technique, were interviewed to explore and prioritize challenges threatening agricultural sustainability in the west of Iran. Findings indicated water scarcity and low productivity beside environmental and climate disasters were the most important challenges from the viewpoint of the participants. Moreover, insufficient investment in the agricultural sector and management weakness at the macro and micro levels were other significant challenges from the perspective of experts. Results of exploratory factor analysis indicated that the challenges threatening agricultural sustainability can be divided into nine categories including lack of investment and liquidity; environmental and climate disasters; scientific weakness; weakness of labor force in the agricultural sector; management problems; weakness of information systems; low agricultural productivity and lack of attention to quality; challenges related to agricultural inputs; and global challenges. This 9-factor structure, which confirmed through confirmatory factor analysis, was able to explain 67.52% of the variance related to the challenges threatening agricultural sustainability in the west of Iran.