The Jurassic Chon Aike Silicic Large Igneous Province (Patagonia and the Antarctic Peninsula) is dominated by voluminous, crust-derived magmas (235,000 km3) that erupted as predominately explosive silicic material over ~40 m.y. In this study, we combine petrological descriptions and bulk-rock major- and trace-element compositions with quartz oxygen-isotope measurements from multiple silicic units (primarily ignimbrites and some rhyolitic flows) from two of the five silicic formations in Patagonia. We have identified that quartz oxygen-isotope values are high (>9‰–12‰). Quartz pheno crysts analyzed by secondary ion mass spectroscopy (SIMS) are also homogeneous at the microscale with no measurable change in isotope value with respect to internal and often complex zoning textures. The ubiquity of widespread high δ18O rhyolites and their trace-element compositions support their origin from melting of a metasedimentary source with a similarly high δ18O value. Mass balance calculations require that an average of >75% melt derived from partial melting of the dominant basement lithology is needed to explain the isotopic and chemical composition of the rhyolites. The ideal P-T environment was identified by thermodynamic models for fluid-absent melting of graywackes at 900 °C and 5 kbar. Regional-scale crustal melting occurred during a widespread, high heat-flux environment within an extensional setting during the breakup of the Gondwanan supercontinent. The overlap of a unique tectonic and igneous environment, combined with a fertile crust dominated by graywacke and pelitic compositions in southern Patagonia, generated large volumes of some of the highest δ18O silicic magmas documented in the geologic record.