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• Accelerated tree growth coincided with increased water-use efficiency in mature Qinghai spruce. • Nitrogen availability positively affected tree growth from 1920 to 2000. • Tree-ring δ15N and C/N values have decreased synchronously since 1965 onwards. • Tree growth enhancement in 2003–2019 was driven by CO 2 fertilization, not by nitrogen availability. Terrestrial vegetation growth is stimulated by rising atmospheric CO 2 concentration, a warmer climate, and increased soil nutrient availability. However, as plants age, progressive nutrient limitation is known to occur, especially in mature forests where soil nitrogen is deficient. Yet the long-term growth response of mature trees to rising CO 2 accompanied by changing climate and nitrogen availability in semi-arid mountain regions is unclear. Here we used tree-ring widths and stable carbon (δ13C) and nitrogen (δ15N) isotopes to investigate the drivers of radial growth of mature Qinghai spruce (Picea crassifolia) in the central Qilian Mountains, northwest China, from 1840 through 2019. Tree growth benefited from improved nitrogen availability, chiefly via changes in bioavailable nitrogen pools modified by a favorable climate during 1930–1964. Enhanced intrinsic water-use efficiency (iWUE), driven by reduced stomatal conductance (g s) related to water deficit, lead to radial growth declines in 1985–2002. Recent acceleration of tree growth was largely attributed to a CO 2 fertilization effect through enhanced iWUE during 2003–2019. Nitrogen availability was positively related to tree growth from the 1920s onward until greater CO 2 fertilization ensued from 2000 onward. Hence, the negative effects of low nitrogen availability on growth could be mitigated or reversed by a high atmospheric CO 2 concentration and warmer climate conditions. Our results suggest that mature spruce forests still harbor potential to increase ecosystem-level carbon sequestration and thereby partially mitigate climate warming. Such a nature-based solution in drought-prone forests would be achieved under warmer-wetter climate conditions in northwest China. [ABSTRACT FROM AUTHOR]