More efficient use ofwater in agricultural systemsis widely needed. However, most irrigated systems are characterized by heterogeneous climate and soil conditions that interact strongly with irrigation management, making optimal irrigation decisions difficult to achieve. Here we investigated the impact of reduced irrigations on spring wheat yields in the Yaqui Valley of Mexico, a region experiencing increased water scarcity. Two years of field experiments containing three irrigation treatments each were used to evaluate the CERES-wheat crop model, with good agreement between observed and modeled yields. The model was then used in a sensitivity analysis whereby seven irrigation strategies were applied across a range of possible soil and climatic conditions. Results indicated that yield losses from reduced irrigations depend greatly on year, corresponding to large variations in rainfall between growing seasons. Estimates of the best timing strategy for a given number of irrigations were more robust with respect to climate variability. Soils also exhibited a strong interaction with irrigation, with the difference between initial soil moisture and wilting point deemed particularly important in this system. The optimal economic strategy was determined for each hypothetical soil based on the observed historical distribution of growing season climatic conditions. The results of this study demonstrate the need to consider soil and climate variability when interpreting experimental results, and the ability of the CERES model to serve this need by quantifying the relative importance of different heterogeneous factors.