| Summary: | With global warming and increasing human activities, exploring the impact of the rising atmospheric carbon dioxide concentration and climate change on forest ecosystems is crucial. In this study, we focus on Euphrates poplar (<i>Populus euphratica</i> Oliv.) in the upper reaches of the Tarim River in the Alaer region of Xinjiang. We use dendrochronological methods, tree-ring width, and stable carbon isotope series to explain basal area increment (BAI) and intrinsic water use efficiency (iWUE) changes. We further explore the influence of past climate change and human activities on the radial growth and iWUE of <i>P. euphratica</i> through stable oxygen isotope analysis combined with historical literature records. The results showed that relative humidity had an essential effect on Δ<sup>13</sup>C and δ<sup>18</sup>O fractionation in <i>P. euphratica</i> tree rings, whereas the vapor pressure deficit (VPD) was considered the main factor influencing the inter-annual variability of the iWUE and BAI. Since 1850, long-term variations in iWUE have exhibited an upward trajectory correlated with rising atmospheric CO<sub>2</sub> levels. Approximately 13% of this iWUE increase can be attributed to changes in carbon-concentration-induced water use efficiency (<sup>cc</sup>iWUE). Although Δ<sup>13</sup>C and δ<sup>18</sup>O were generally uncorrelated between 1850 and 2018, around 1918, their relationship changed from being weakly correlated to being significantly negatively correlated, which may record changes related to the upstream Tarim River diversion. During the period from 1850 to 2018, both the BAI and iWUE showed an increasing trend for <i>P. euphratica</i> growth; however, the relationship between them was not stable: during 1850–1958, both variables were mainly influenced by climatic factors, while during 1959–2018, the most important influence was due to human activities, specifically agricultural development and irrigation diversions. An abrupt surge in the BAI was observed from 1959 to 1982, reaching its peak around 1982. Surprisingly, post-1983, the escalating iWUE did not correspond with a continuation of this upward trajectory in the BAI, highlighting a divergence from the previous trend where the enhanced iWUE no longer facilitated the growth of <i>P. euphratica.</i> Despite <i>P. euphratica</i> having adapted to the continuously rising C<sub>a</sub>, improving its iWUE and growth capacity, this adaptive ability is unstable and may easily be affected by human activities. Overall, the increase in C<sub>a</sub> has increased the iWUE of <i>P. euphratica</i> and promoted its growth at a low frequency, while human activities have promoted its development at a high frequency.
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