Isotopic and geochemical evidence of paleoclimates, especially for the last glaciation, has been obtained from deep confined groundwaters of southern India. The d13C, d18O, chloride, and deuterium analyses of groundwaters show distinct excursions inferred to be related to climatic variations. The arid climatic episode associated with the last glaciation (18,000 ± 2000 yr B.P.) is conspicuously identified by signatures of relatively enriched d13C (-10 to -12‰ PDB) and d18O (-5.3 to -4.8‰ SMOW) values, and high chloride concentration (80 to 160 mg/l). The transition from an arid to humid period ca. 12,000–8000 yr B.P. is shown by a decreasing trend in the d13C (-9.5 to -17‰) and d18O (-4.5 to -6.3‰) contents of groundwaters. The late Holocene (since 4000 yr B.P.), marked by a more humid but unstable climate, is identified by further depletion of d13C (-13 to -20‰) and d18O (-5.2 to -6.3‰). Similar variation between d18O and chloride values in confined groundwaters further demonstrates two distinct climatic excursions (arid and humid) governed by the “amount effect.” This is the first time that isotopic and geochemical signatures related to changing paleoclimates have been identified in the confined groundwaters of the southern Indian landmass.