Predicting how increasing atmospheric CO2 will affect the hydro-logic cycle is of utmost importance for a range of applications rang-ing from ecological services to human life and activities. A typical perspective is that hydrologic change is driven by precipitation andradiation changes due to climate change, and that the land surface willadjust. Using Earth system models with decoupled surface (vegetation physiology) and atmospheric (radiative) CO2 responses, we hereshow that the CO2 physiological response has a dominant role inevapotranspiration and evaporative fraction changes and has a major effect on long-term runoff compared with radiative or precipitation changes due to increased atmospheric CO2. This major effect is true for most hydrological stress variables over the largest fraction of the globe, except for soil moisture, which exhibits amore nonlinear response. This highlights the key role of vegetationin controlling future terrestrial hydrologic response and emphasizes that the carbon and water cycles are intimately coupled over land.