Water availability in the dry Western United States (US) under a warming climate and increasing water use demand has become a serious concern. Previous studies have projected future runoff changes across the Western US but ignored the impacts of ecosystem response to elevated CO2 concentration. Here, we aim to understand the impacts of elevated CO2 on future runoff changes through ecosystem responses to both rising CO2 and associated warming using the Noah-MP model with representations of vegetation dynamics and plant hydraulics. We first validated Noah-MP against observed runoff, LAI, and terrestrial water storage anomaly from 1980–2015. We then projected future runoff with Noah-MP under downscaled climates from three climate models under RCP8.5. The projected runoff declines variably from the Pacific Northwest by –11% to the Lower Colorado River basin by –92% from 2016–2099. To discern the exact causes, we conducted an attribution analysis of two additional sensitivity experiments: one with constant CO2 and another with monthly LAI climatology based on the Penman-Monteith equation. Results show that surface “greening” (due to the CO2 fertilization effect) and the stomatal closure effect are the second largest contributors to future runoff change, following the warming effect. These two counteracting CO2 effects are roughly compensatory, leaving the warming effect to remain the dominant contributor to the projected runoff declines at large river basin scales. This study suggests that both surface “greening” and stomatal closure effects are important factors and should be considered together in water resource projections.