Groundwater is the second largest store of freshwater in the world. The sustainability of the ecosystem is largely dependent on groundwater availability, and groundwater has already been under tremendous pressure to fulfill human needs owing to anthropogenic activities around various parts of the world. The footprints of human activities can be witnessed in terms of looming climate change, water pollution, and changes in available water resources. This paper provides a comprehensive view of the linkage between groundwater, climate system, and anthropogenic activities, with a focus on the Indian region. The significant prior works addressing the groundwater-induced response on the climatic system and the impacts of climate on groundwater through natural and human-instigated processes are reviewed. The condition of groundwater quality in India with respect to various physicochemical, heavy metal and biological contamination is discussed. The utility of remote sensing and GIS in groundwater-related studies is discussed, focusing on Gravity Recovery and Climate Experiment (GRACE) applications over the Indian region. GRACE-based estimates of terrestrial water storage have been instrumental in numerous groundwater studies in recent times. Based on the literature review, the sustainable practices adopted for optimum utilization of groundwater for different purposes and the possible groundwater-based adaptation strategies for climate change are also enunciated.