The response of hydrologic circulation to climate and land use changes is important in studying the historical, present, and future evolution of aquatic ecosystems. In this study, the Coupled Model Inter-comparison Project Phase 5 multi-model ensemble and a raster-based Xin'anjiang model were applied to simulate future streamflows under three climate change scenarios and two land use/cover change conditions in the Xinjiang Basin, China, and to investigate the combined effect of future climate and land use/cover changes on streamflow. Simulation results indicated that future climate and land use/cover changes affect not only the seasonal distributions of streamflow, but also the annual amounts of streamflow. For each climate scenario, the average monthly streamflows increase by more than 4% in autumn and early winter, while decreasing by more than −26% in spring and summer for the 21st century. The annual streamflows present a clear decreasing trend of −27%. Compared with land use/cover change, climate change affects streamflow change more. Land use/cover change can mitigate the climate change effect from January to August and enhance it in other months. These results can provide scientific information for regional water resources management and land use planning in the future.