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Leaf anatomical traits are susceptible to environmental changes and can reflect plant adaptation strategies to the environment. Populus euphratica plays a key role in maintaining ecosystem processes and functions in arid zones, but the variations in leaf anatomical traits of Populus euphratica and their drivers at large scales remain unclear. Here, we investigated 10 leaf anatomical traits of Populus euphratica from 12 sampling sites in the arid zone of China, and explored how they were affected by geographic, climatic, and soil factors. Our results showed that these traits differed significantly between sites (P < 0.05), which was mainly determined by climate and soil factors that together explained 41.4 % of the trait variation. The impact of climate factors is the most critical, as they can directly influence the variation in leaf anatomical traits and indirectly affect trait variation by influencing soil factors. Among them, the max temperature of the warmest month (BIO5), soil available phosphorus (SAP) and soil moisture content (SM) had the most critical effect. Besides, temperature was the major influencing factor for the ratio of spongy tissue thickness to leaf thickness (SR), palisade tissue thickness (PT), the ratio of palisade tissue thickness to spongy tissue thickness (PSR), and the ratio of palisade tissue thickness to leaf thickness (CTR), while soil nutrient was the major influencing factor for leaf thickness (LT), lower epidermis thickness (LET), and spongy tissue thickness (ST). Our results provide important insights into the response of dryland forests to climate change, and suggest that climate warming and declining soil quality may have a stronger effect on Populus euphratica.