The groundwater vulnerability (GV) assessment for contamination is an effective technique for the planning, policy, and decision-making, as well as for sustainable groundwater resource protection and management. The GV depends strongly on local hydrogeological settings and land-use conditions that may vary in response to the activities of agricultural development. In this study, a modified DRASTIC model, which employs an additional factor of land use coupled with the analytic hierarchy process (AHP) theory, was used to quantify the spatial and temporal variation of GV and groundwater contamination risk in the Pingtung groundwater basin. The results show that the GV slightly decreased due to the decrease in agricultural areas under the change of land use over two decades (1995–2017). The yearly changes or a shorter period of observations incorporated with the accurate land-use map in DRASTIC parameters could improve GV maps to obtain a better representation of site-specific conditions. Meanwhile, the maps of yearly contamination risk indicated that the counties of Jiuru and Ligang are at high risk of nitrate pollution since 2016. In other agriculture-dominated regions such as Yanpu, Changzhi, and Gaoshu in the Pingtung groundwater basin, the climate conditions influence less the temporal variations of groundwater contamination risk. The results of this study are expected to support policy-makers to adopt the strategies of sustainable development for groundwater resources in local areas.