This paper analyzes the impacts of climate change and human pressures on Yazd-Ardakan aquifer using the Hadley Centre Coupled Model, version 3 (HADCM3) circulation Model and A2 emission scenario. Water levels in the study aquifer were simulated using three-dimensional finite-difference groundwater model (MODFLOW 2000) with GMS 8.3 as pre- and postprocessing software. Input for groundwater recharge time series under the climate change scenarios were derived using a regression equation based on the cumulative deviation from mean rainfall using MATLAB. Human pressures on the aquifer were modeled through climate change impacts on water requirements of cultivated areas. Three scenarios were simulated to represent the effects of climate change and human pressures on aquifer storage and hydraulic head. Climate change and human pressures (scenario 1) will reduce aquifer storage and result in decreasing hydraulic head by −0.56 m year−1. Reduction in pumping water under scenario 2 (irrigation system modification) and scenario 3 (irrigation system modification and cropping patterns) will result in groundwater level fluctuation of about −0.32 and 0.08 m year−1, respectively. Scenario 3 is capable of restoring and protecting the groundwater resources in Yazd-Ardakan aquifer. The results of this study are useful to obtain sustainable groundwater management in Yazd-Ardakan aquifer.