Abstract: Under the pressures of climate change and water scarcity, arid regions in Northwest China urgently need to coordinate grain production improvement with agricultural water conservation. This study constructed an integrated scenario matrix combining three climate change scenarios, SSP1-2.6, SSP2-4.5, and SSP3-7.0, with five irrigation layout scenarios, I0～I4. The AquaCrop model was used to evaluate the water-use reduction potential, water footprint reduction potential, and production increase potential of wheat and maize in the Shiyang River Basin, and to identify the optimal spatial pattern of irrigation layouts. The results showed that the future climate exhibited a “pseudo warm-wet” tendency, with a mismatch between increased precipitation and the critical crop water demand period. Improved green water use enabled wheat to achieve certain production increases and water footprint reductions, whereas maize showed a strong tendency toward increased water consumption accompanying yield gains. The optimal irrigation layout in the basin was generally characterized by “micro-irrigation as the core and region-specific adaptation,” which could increase grain production by 6.6%～95.1% and reduce the water footprint by less than 11.3%, but would increase blue water consumption by 40.1%～132.2%. Therefore, the basin should strictly control total water use while promoting water-saving irrigation, and advance drought-resistant maize breeding to support refined climate-adaptive agricultural water resources management.