Water management substantially alters natural regimes of streamflow through modifying retention time and water exchanges among different components of the terrestrial water cycle. Accurate simulation of water cycling in intensively managed watersheds, such as the Yakima River basin (YRB) in the Pacific Northwest of the US, faces challenges in reliably characterizing influences of management practices (e.g., reservoir operation and cropland irrigation) on the watershed hydrology. Using the Soil and Water Assessment Tool (SWAT) model, we evaluated streamflow simulations in the YRB based on different reservoir operation and irrigation schemes. Simulated streamflow with the reservoir operation scheme optimized by the RiverWare model better reproduced measured streamflow than the simulation using the default SWAT reservoir operation scheme. Scenarios with irrigation practices demonstrated higher water losses through evapotranspiration (ET) and matched benchmark data better than the scenario that only considered reservoir operations. Results of this study highlight the importance of reliably representing reservoir operations and irrigation management for credible modeling of watershed hydrology. The methods and findings presented here hold promise to enhance water resources assessment that can be applied to other intensively managed watersheds.