In the traditional CMIP approach, human system information required as forcing for climate prediction is generated in advance by economic integrated assessment models (IAMs) that include both energy and agricultural sectors and passed to earth system models in an asynchronous fashion. An integrated Earth System Model (iESM), which combines the Global Change Assessment Model, Global Land-use Model, and community Earth System Model, was recently developed (Collins et al. 2015; Thornton et al., 2017). This synchronous (coupled) approach provides a tremendous opportunity for modeling experiments to examine interactions between the human and natural systems. A series of experiments was performed using the iESM under the RCP8.5 scenario to explore the radiative and physiological effects of atmospheric CO2 concentration and Earth-human interactions in the context of future hydrological projections. We found that CO2 concentration has significant effects on the hydrological cycle by modulating the evapotranspiration of the plant and soil system. Including Earth and human system interactions also has significant impacts on future water cycle through interactive land use and land cover change, greenhouse gas emissions, and water management. On the basis of these results, we suggest utilizing more integrated modeling systems to better project future environmental changes.