Groundwater extraction at rates exceeding recharge is occurring throughout Iran for agricultural and industrial activities, resulting in land subsidence in many areas, particularly the Yazd-Ardakan Plain (YAP) in the dry and desert regions of central Iran. In this study, Interferometric Synthetic Aperture Radar (InSAR) time series analysis and statistical models are used to characterize the controls on land subsidence in the YAP, from 2003 to 2020. Our results reveal the existence of a northwest-southeast elongated area of 363 experiencing subsidence at rates up to 15 cm/yr. In the YAP, the international Airport, railway, transit road, and several industrial and historical sites are threatened by the differential subsidence. Well data confirm that groundwater levels have decreased by 18 meters between 1974 and 2018, driving the compaction of sediments within the underlying aquifer system. Our statistical analysis shows that the thickness of a shallow, clay-rich aquitard layer controls the extent of the observed subsidence and an Independent Component Analysis of the InSAR time series shows that inelastic compaction dominates. This work reveals that in central Iran, current groundwater extraction practices are not sustainable and result in permanent subsidence, ground fractures with impact on infrastructures, and a permanent decrease in water storage capacity.