The Paraná-Etendeka large igneous province (PELIP) covers ca. 1.5 million km2 in South America and Africa. Its voluminous continental basalt flows are related to the opening of the South Atlantic Ocean in the Early Cretaceous (~135-132 Ma). In South America, the geochemical and petrological evolution of the PELIP has been extensively studied in Brazil, where the largest exposures are found, while the Uruguayan portion remains less studied. We conducted a multidisciplinary study on the Uruguayan lavas, which host the world-class amethyst-agate deposits of Los Catalanes. Our study integrates field observations, petrography (including cathodoluminescence microscopy), whole-rock geochemistry, isotopic compositions, and mineral chemistry, to provide new insights into the magmatic evolution of the PELIP in Uruguay, and its role in conditioning the system for secondary silica mineralisation. Unaltered lava levels show loss on ignition (LOI) <2 wt.%, and support our petrogenetic interpretation. The lavas are low-Ti tholeiites and range in composition from basaltic andesite to andesite. They are enriched in incompatible elements relative to MORBs and present “arc-like” trace element patterns, such as Large-Ion Lithophile Elements enrichment relative to High-Field Strength Elements, and negative Nb anomalies. The trace element patterns and Sr, Nd, and Pb isotope signatures suggest an enriched mantle source subsequently modified by magma-crust interaction. On the other hand, amethyst-hosting levels within individual flows show higher LOI (up to 9 wt.%) and lower Ca, Mg and Al concentrations, suggesting low-temperature hydrothermal alteration and/or weathering. The association between mineralised geodes and altered lavas demonstrates that the silica mineralisation was controlled by pervasive fluid infiltration.