Multivariate statistical analysis has been proven an invaluable tool for environmental studies. In the present hydrogeochemical study of Eastern Central Greece and NW Euboea (Evia) Island, several statistical tools were applied, i.e. one-way analysis of variance (ANOVA), cluster analysis and principal component factor analysis alongside the classical hydrogeochemical approach in order to assess the hydrogeochemical features and evaluate the impact of anthropogenic and geological factors on groundwater chemistry. The area is characterized by the presence of ophiolitic ultramafic rock, carbonate rocks, post-Alpine sediments and hot springs with travertines, while the main anthropogenic activity is irrigation. A total of 85 groundwater samples were collected and analyzed, which were found to be enriched in Cr (3 μg/L), Ni (2.2 μg/L), Fe (4.2 μg/L), Mg (32.5 mg/L), Cl (31 mg/L), SO42- (36 mg/L) and NO3- (9.7 mg/L) compared to the median values of European and Greek streams and groundwaters. Based on the results and the statistical analysis, four main factors have been identified controlling the composition and quality of the groundwater, i.e. seawater intrusion on the groundwater aquifers in the coastal areas, intense use of fertilizers in cultivated areas, the influence of the carbonate and the ophiolitic ultramafic rocks. The hydrothermal system and its depositions, which exist in the study area, seem to have not played any major role in the controlling of the chemical composition of the cold groundwater aquifers. The statistical assessment of hydrogeochemical data alongside the classical hydrogeochemical approach is recommended in future studies, combined with efforts to develop new tools that help a deeper understanding of groundwater characteristics.