Variations in lithium and silicon isotope ratios in groundwaters of the Great Artesian Basin in Australia, and the causes of these variations, have been explored. The chemistries of Li and Si in groundwater are influenced by the dissolution of primary phases, the formation of secondary minerals, and the reaction of solid phases with dissolved constituents, while isotopic variations are generated by uptake into clays, which preferentially incorporate the light isotopes. The lithium isotopic composition (expressed as δ7Li) of the groundwaters ranges from +9 to +16%, and clearly reflects changes in aquifer conditions. Reaction-transport modelling indicates that changes in Li concentrations are principally controlled by the ratio of the weathering rate of primary minerals to the precipitation rate of secondary minerals, whereas δ7Li is affected by the extent of isotope fractionation during secondary mineral formation (which is dependent on mineralogy). The patterns of groundwater Si concentrations and δ30Si values versus flow distance suggest that Si is at steady state in the aquifer. The δ30Si value of most of the groundwater samples is close to -1%, which is significantly lower than the δ30Si value of the reservoir rocks (~0%). Since precipitation of clays preferentially removes the light Si isotopes from solution, the most plausible explanation for these low groundwater δ30Si values is addition of Si by dissolution of isotopically light secondary minerals. These data, together with model calculations, show that Li isotopes are extremely sensitive to changes in the chemical and physical conditions in the aquifer, whereas Si is not. Importantly, the model suggests that even in large aquifers with long fluid residence times, where steady-state would be expected to be reached, the concentrations and isotopic fractionation of trace elements are not controlled by Li adsorption. The model developed here provides a basis for using Li isotopes measured in groundwaters and surface waters to constrain weathering processes.