Water management activities modify water fluxes at the land surface and affect water resources in space and time. Conventional understanding on the role of water management suggests that regulated river flow would be less sensitive to future climate conditions than natural flow in terms of the absolute changes in mean monthly flows. In this study the authors evaluate such an assumption by redefining sensitivity as the difference in the emergence of changes in cumulative distribution functions (CDFs) of future regulated and natural flows in response to climate change with respect to their respective historical regulated and natural flow conditions. The emergence of changes (shift in CDFs) in natural and regulated river flow regimes across the western United States from simulations driven by multiple climate models and scenarios were compared. Forty percent of Hydrologic Unit Codes 4 (HUC4s) over the western United States might perceive such a shift in seasonal regulated flow earlier than they would have seen in natural flow conditions, although the absolute change is smaller than that under natural conditions. About 10% of the regulated HUC4s see a delay and are therefore less sensitive to climate change. In the spring (MAM), the overall sensitivity tends to decrease as the level of river regulation increases, as expected. However, in the winter (DJF) and summer (JJA) seasons, the sensitivity tends to increase with increasing levels of regulation, with changes in smaller magnitudes than under natural conditions. The results could inform integrated assessment studies when designing adaptation strategies in the water–energy–food nexus.