The integration of water management in integrated assessment and Earth system models at the regional scale is an important step toward improving our understanding of the interactions between human activities, terrestrial system and water cycle, and to evaluate how system interactions are affected by a changing climate at the regional scale. This integration is critical to investigate the implications of climate change impacts and adaptation and mitigation options on water resources (e.g., balances between water demand and supply) in the U.S., and how water constraints can feedback to influence other human decisions and physical processes. The work has focused on several primary goals: 1) the development of a regional representation of water demands in the Global Climate Assessment Model (GCAM), and 2) the linkage of GCAM and the land surface component of Regional Earth System Model (RESM) ‰ÛÒ including the Community Land Model (CLM), the MOdel for Scale Adaptive River Transport (MOSART), and the Water Management (WM) components ‰ÛÒ to eventually propagate human decisions pertaining to water demand per sector and technology from the GCAM decision framework to RESM at the appropriate temporal and spatial scales. These two goals required a careful effort in representing the interaction pathways in the integrated water cycle among GCAM and RESM (i.e., CLM-MOSART-WM) and in addressing any inconsistency in representing the integrated water cycle. The coupled framework was initially demonstrated over the Midwest Pilot Region (Missouri, Upper Mississippi, and Ohio) and is currently being extended to cover the continental United States. Implications for future flow regulation, water supply, and supply deficit are investigated using climate change projections with multiple emission scenarios, which affect both natural flow and water demand. Over the Midwest, changes in flow regulation are mostly driven by the change in natural flow due to the limited storage capacity over the Ohio and Upper Mississippi river basins. Over the Missouri river basin however the change in demand is driving the long term change in flow regulation while the change in natural flow drives the decadal variability.