AquaCrop is a water-driven model that simulates the effect of environment and management on crop production under deficit irrigation. The model was calibrated and validated using three databases and four irrigation treatments (i.e., 100%ET, 80%ET, 70%ET, and 50%ET). Model performance was evaluated by simulating canopy cover (CC), biomass accumulation, and water productivity (WP). Statistics of root mean square error (RMSE) and Willmott’s index of agreement (d) showed that model predictions are suitable for non-stressed and moderate stressed conditions. The results showed that the simulated biomass and yield were consistent with the measured values with a coefficient of determination (R2) of 0.976 and 0.950, respectively. RMSE and d-index values for canopy cover (CC) were 2.67% to 4.47% and 0.991% to 0.998% and for biomass were 0.088 to 0.666 ton/ha and 0.991 to 0.999 ton/ha, respectively. Prediction of simulated and measured biomass and final yield was acceptable with deviation ˂10%. The overall value of R2 for WP in terms of yield was 0.943. Treatment with 80% ET consumed 20% less water than the treatment with 100%ET and resulted in high WP in terms of yield (0.6 kg/m3) and biomass (1.74 kg/m3), respectively. The deviations were in the range of −2% to 11% in yield and −2% to 4% in biomass. It was concluded that AquaCrop is a useful tool in predicting the productivity of cotton under different irrigation scenarios.