Long-term excessive groundwater exploitation for agricultural, domestic and stock applications has resulted in substantial ground subsidence in Arizona, USA, and especially in the Willcox Groundwater Basin. The land subsidence rate of the Willcox Basin has not declined but has rather increased in recent years, posing a threat to infrastructure, aquifer systems, and ecological environments. In this study, we first investigate the spatiotemporal characteristics of land subsidence in the Willcox Groundwater Basin using an interferometric synthetic aperture radar (InSAR) time series analytical approach with L-band ALOS and C-band Sentinel-1 SAR data acquired from 2006 to 2020. The overall deformation patterns are characterized by two major zones of subsidence, with the mean subsidence rate increasing with time from 2006 to 2020. An approach based on independent component analysis (ICA) was adopted to separate the mixed InSAR time series signal into a set of independent signals. The application of ICA to the Willcox Basin not only revealed that two different spatiotemporal deformation features exist in the basin but also filtered the residual errors in InSAR observations to enhance the deformation time series. Integrating the InSAR deformation and groundwater level data, the response of the aquifer skeletal system to the change in hydraulic head was quantified, and the hydromechanical properties of the aquifer system were characterized. Historical spatiotemporal storage loss from 1990 to 2020 was also estimated using InSAR measurements, hydraulic head and estimated skeletal storativity. Understanding the characteristics of land surface deformation and quantifying the response of aquifer systems in the Willcox Basin and other groundwater basins elsewhere are important in managing groundwater exploitation to sustain the mechanical health and integrity of aquifer systems.