Water management in agriculture is impossible without considering the relationships between water, soil, and plants. Simulation models are a valuable tool for improving water management in the field and increasing water productivity. It is essential to evaluate the efficiency of the model in each region and for each crop. In order to validate the AquaCrop model in Birjand region, an experiment was conducted in a randomized complete block design as a factorial, in which two factors of irrigation water salinity at two levels (S1, S2, respectively equivalent to 6 and 1.6 dS/m) and irrigation water quantity at four levels (I1, I2, I3, and I4, respectively equivalent to 50, 75, 100, and 125 percent of plant water requirement) were implemented in two crop years 2017-18 and 2018-19. Initially, the model was calibrated for each salinity and drought treatment simultaneously for the first-year data and then validated simultaneously for the salinity and drought treatments for the second-year data. The simulation values were evaluated based on the measured values of grain yield and total biomass using five evaluation indices including root mean square error (RMSE), coefficient of determination (R2), efficiency factor (EF), maximum error (ME), and residual coefficient (CRM). The results of RMSE values of 0.19 t/ha in the calibration stage and 0.3 t/ha in the validation stage showed that the AquaCrop model simulated biomass and grain yield for wheat well under salinity and water deficit conditions.