Lake Tana basin encompasses a wide regional volcanic aquifer system, in the northwestern highlands of Ethiopia. It has significant water resource potential for water supply and irrigation purposes. The objective of this study was to assess the physiochemical characteristics of the surface water-groundwater and investigate the processes controlling groundwater chemistry. A total of 273 water samples were collected from different water points for major ions and stable isotope analysis, representing different physiographic and hydrogeologic regions. Multivariate statistical, graphical methods, saturation and speciation modelling were used jointly to characterize water chemistry and to define hydrogeochemical processes. The Piper plots in combination with cluster analysis and isotope hydrological data indicate that, generally, the groundwater chemistry of the basin can be classified into (1) low TDS Ca-HCO3, Ca-Mg-HCO3, and Ca-Na-Mg-HCO3 type water which is relatively enriched in δ18O-δ2H and depleted in δ13C. These are recharge waters, which are characterized by low rock-water interaction; (2) brackish Mg-Na-Ca-HCO3 type water which is relatively depleted in δ18O-δ2H and enriched in δ13C; and (3) low TDS Na-(Ca)-HCO3 and Na-HCO3 type water which varies from less to more depleted in δ18O-δ2H and is characterized by relatively enriched δ13C. The cross-plots of the major cations vs. HCO3- and stability diagrams show that the primary processes controlling the groundwater evolution in the Lake Tana basin are alumino-silicate weathering and dissolution. Studying the hydrogeochemical characteristics of a complex geologic system with integrated approach helps to understand the complex groundwater flow system and flow dynamics, which in turn helps for proper groundwater utilization and future management.