The Water Framework Directive (WFD) requires EU member states to assess the chemical status of groundwater bodies, a status defined according to threshold values for harmful elements and based on/the natural background level (NBL). The NBL is defined as the expected value of the concentration of elements naturally present in the environment. The aim of this study is to propose a methodology that will be broadly applicable to a wide range of conditions at the regional and national scale. Using a statistical approach, the methodology seeks to determine NBLs for SO4, As, Cd, Cr, Cu, Ni, Zn, and F based on the lithology of aquifers from which groundwater monitoring data were collected. The methodology was applied in six EU countries to demonstrate validity for a wide range of European regions. An average concentration was calculated for each parameter and chosen water point and linked to a lithology. Based on the dataset created, significant differences between lithologies and pressure categories (urban, agricultural, industrial, and mining) were tested using a nonparametric test. For each parameter, 90th percentiles were calculated to provide an estimation of the maximum natural concentrations possible for each lithology.