Vegetation change affects water fluxes and influences the direction and intensity of salt exchange between ecosystems and groundwater. In some conditions it can also lead to an intense accumulation of salts in soils and aquifers, as has been documented for the conversion of native grassland to tree plantations in the plains of Argentina, Hungary and Russia. In this paper we present a hierarchical framework to predict salt accumulation following vegetation change that is based on climatic, hydrogeological and biological factors. We evaluated this spatially explicit framework in temperate South America using a network of 32 pairs of adjacent plantation and grassland stands studied with detailed field measurements and remotely sensed imagery from MODIS. Our sites cover a broad precipitation gradient (770 to 1500 mm a−1) and are underlain by shallow water tables (<2.5 m of depth). At the regional scale, geoelectric surveying revealed that the salinization of plantation soils depended strongly on climate, occurring only where the annual water balance (mean precipitation-Penman-Monteith potential evapotranspiration) was <100 mm a−1 (p < 0.0001, n = 24). At the local scale, we observed that groundwater salinities observed under ∼50-year old plantations of different species were associated with their tolerance to salinity (p < 0.001, n = 10). Salinization occurred rapidly where rainfall was insufficient to meet the water requirements of tree plantations and where groundwater use compensated for this deficit, driving salt accumulating in the ecosystem. A general understanding of the vegetation-groundwater relationship will help predict and manage the negative and positive consequences of groundwater use from stand to regional levels of analysis.