Suquia River is a medium-sized hydrological system (basin area of ~7,700 km2) that supplies fresh water to Cordoba city, a town of ~1,500,000 inhabitants in central Argentina. This paper examines the present-day hydrochemistry of Suquia River urban catchment analyzing its major and minor dissolved components, and the nutrients variability by means of QUAL-2K modeling software. The Suquia River has bicarbonate-type waters upstream the city and sulfate-type waters right downstream, whereas they exhibit a mixed-to-alkali-type cationic composition. The seasonal analysis of its major dissolved constituents clearly showed a dilution process during the wet season (i.e. austral summer). In the last 20 years, the Suquia River has modified its anionic composition, now showing higher relative concentrations of SO42− as a consequence of urban activities. However, trace elements dissolved concentrations do not evidence a strong pollution effect. Nutrients [nitrogen species, total phosphorous (TP)] and related parameters, such as biochemical oxygen demand (BOD), and dissolved oxygen (DO), evidence a clear influence of human activities. The QUAL-2K model was used to evaluate the spatial behavior of selected nutrients and associated variables, (i.e. TP, N–NH4+, N–NO3−, DO, BOD). Nutrient concentrations are affected by point sources of contaminants, particularly domestic waste and sewage, as well as by diffuse agricultural pollution. A calibrated QUAL-2K modeling exercise clearly shows the impact of the Cordoba city’s municipal wastewater treatment plant on the Suquia River water quality.