The western Great Artesian Basin (GAB) is an important water source for pastoral and town water supplies, as well as for springs containing endemic flora and fauna, within arid Australia. This study focuses on the hydrochemical variations of groundwater and spring discharge in order to determine the major geochemical processes responsible for water quality and evolution across the western GAB. Regional hydrochemical trends within groundwater generally support the modern groundwater potentiometric surface and interpreted flow paths, highlighting that these approximately represent the long-term flow paths. Additionally, the regional chemical variations along the flow paths in the western GAB are complex, with their composition being a function of several controlling processes, including location of recharge, evapo-concentration, mixing and various water–rock interactions. These processes cause groundwater east of Lake Eyre to be predominantly of Na-HCO₃ type, whereas groundwater originating from the western margin is of Na-Cl-(-SO₄) type. The GAB springs appear to be discharging water predominantly from the main GAB aquifer, the J Aquifer; however, a component of the discharging water from several springs is from a source other than the J Aquifer. Current understanding of the hydrochemical variations of groundwater and spring discharge of the western GAB can help provide constraints on groundwater flow, as well as provide an understanding of the geochemical and hydrological processes responsible for water quality evolution.