In order to explore the water-fertilizer management strategy suitable for maize growth in the Hetao Irrigation District, Inner Mongolia, this study conducted a field experiment with different irrigation and fertilization levels. After the calibration and validationby observed data, the AquaCrop model was used to simulate the variation pattern of corn yield and water use efficiency (WUE) under different irrigation and fertilization levels. The results indicated:(1) The R² values of simulated and measured canopy coverage and biomass were 0.74~0.99 and 0.87~0.99, respectively, during model calibration and validation. The NRMSE values ranged from 4.55% to 12.32% and 5.77% to 27.07%, respectively, while the E_NS ranged from 0.90 to 0.99 and 0.85 to 0.99 respectively. The R² values between the simulated and measured output values were 0.99 and 0.97, respectively, and NRMSE were 4.59% and 3.42%, and E_NS were 0.95 and 0.97, respectively. The R² between the simulated and measured WUE were 0.81 and 0.86, respectively, and NRMSE were 6.75% and 13.85%, and E_NS were 0.96 and 0.83, respectively, indicating that AquaCrop model had a good applicability in the Hetao Irrigation District. (2) The verified model was used to simulate the effects of irrigation changes on maize yield and WUE at different fertilization levels. The results showed that when irrigation rate reached 270 mm and continued to increase, the maize yield and WUE remained basically unchanged or even decreased. (3) With stable yield and high efficiency as the target, under the medium fertilization, the optimal corn yield and WUE were given at 270 mm of irrigation. Therefore, we recommend 270 mm irrigation, 375 kg/hm² fertilizing as the best combination to ensure the stable-yield and high-efficiency in the studied area.