The Matanza-Riachuelo River Basin is one of the most important in Argentina. The basin supplies water to 13.5% of Argentinian population, though most of the surface water show severe contamination and groundwater is also polluted locally. The aim of this work is to generate scientific knowledge to support future groundwater quality improvement actions. Groundwater chemistry and its origin was studied using a multi-tool approach including (1) multivariate analysis, (2) hydrochemical evolution and solute mass balances along flow lines and (3) hidrogeochemical modelling. The most common chemical type across the whole aquifer system is the Na-HCO3 type, which results from soil CO2 and calcite dissolution, plus cation exchange during or shortly after recharge. On a local scale, saline groundwaters have been identified in two different areas. Strongly saline Cl-Na groundwater in the lower basin is the result of Na-HCO3 water mixing with marine water, probably of Holocene age, encroached in the coastal part of the aquifer. Slightly saline Na-ClSO4 groundwater in the upper basin seem to result from dissolution of sulphate bearing minerals in the top of the Puelches Formation and mixing with water of the deeper Paraná Formation.