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Sustained increase in atmospheric CO _2 is strongly coupled with rising temperature and persistent droughts. While elevated CO _2 promotes photosynthesis and growth of vegetation, drier and warmer climate can potentially negate this benefit, complicating the prediction of future terrestrial carbon dynamics. Manipulative studies such as free air CO _2 enrichment (FACE) experiments have been useful for studying the joint effect of global change factors on vegetation growth; however, their results do not easily transfer to natural ecosystems partly due to their short-duration nature and limited consideration of climatic gradients and potential confounding factors, such as O _3 . Urban environments serve as a useful small-scale analogy of future climate at least in reference to CO _2 and temperature enhancements. Here, we develop a data-driven approach using urban environments as test beds for revealing the joint effect of changing temperature and CO _2 on vegetation response to drought. Using 75 urban-rural paired plots from three climate zones over the conterminous United States (CONUS), we find vegetation in urban areas exhibits a much stronger resistance to drought than in rural areas. Statistical analysis suggests the drought resistance enhancement of urban vegetation across CONUS is attributed to rising temperature (with a partial correlation coefficient of 0.36) and CO _2 (with a partial correlation coefficient of 0.31) and reduced O _3 concentration (with a partial correlation coefficient of −0.12) in cities. The controlling factor(s) responsible for urban-rural differences in drought resistance of vegetation vary across climate regions, such as surface O _3 gradients in the arid climate, and surface CO _2 and O _3 gradients in the temperate and continental climates. Thus, our study provides new observational insights on the impacts of competing factors on vegetation growth at a large scale, and ultimately, helps reduce uncertainties in understanding terrestrial carbon dynamics.