The sustainable use of groundwater has become increasingly challenging due to extreme hydrological events and anthropogenic activity. In this study, the basin-scale groundwater response to precipitation variation was analyzed using an integrated model that comprises lumped models for land and river recharges and a distributed model for groundwater. The integrated model was applied to the Chih-Ben watershed, Taiwan, using 20 years (1988-2007) of data. The hydrological data were analyzed for trends using statistical tests. Based on decreasing trends in precipitation and groundwater levels and an increasing trend in stream flow, the oblique-cut method was applied to precipitation and excess infiltration to assess land and streambed recharge. Distributed numerical groundwater modeling was used to simulate the basin-scale groundwater responses to precipitation variation and anthropogenic pumping. The model was calibrated using stable-isotope and groundwater-level data. The safe yields were estimated for the Chih-Ben watershed for dry, wet, and normal precipitation scenarios. The safe yield of groundwater was shown to vary with precipitation, which does not guarantee the sustainable use of groundwater resources. Instead, water resources should be assessed at a basin scale, taking into account the whole ecosystem, rather than only considering water for human consumption in the alluvium.