This study investigates the effects of irrigation on global water resources by performing and analyzing Community Land Model 4.0 (CLM4) simulations driven by downscaled/bias-corrected historical simulations and future projections from five General Circulation Models (GCMs). For each climate scenario, three sets of numerical experiments were performed: (1) a CTRL experiment in which all crops are assumed to be rainfed; (2) an IRRIG experiment in which the irrigation module is activated using surface water (SW) to feed irrigation; and (3) a PUMP experiment in which a groundwater pumping scheme coupled with the irrigation module is activated for conjunctive use of surface water and groundwater (GW) for irrigation. The parameters associated with irrigation and groundwater pumping are calibrated based on a global inventory of census-based water use compiled by the Food and Agricultural Organization (FAO). Our results suggest that irrigation could lead to two major effects: SW (GW) depletion in regions with irrigation primarily fed by SW (GW), respectively. Furthermore, irrigation depending primarily on SW tends to have larger impacts on low-flow than high-flow conditions, suggesting increased vulnerability to drought. By the end of the 21st century, combined effect of increased irrigation water demand and amplified temporal-spatial variability of water supply may lead to severe local water scarcity for irrigation. Regionally, irrigation has the potential to aggravate/alleviate climate-induced changes of SW/GW although such effects are negligible when averaged globally. Our study highlights the need to account for irrigation effects and sources in assessing regional climate change impacts.