The petrogenesis of calc-alkaline magmatism in the Eocene Absaroka Volcanic Province (AVP) is investigated at Washburn volcano; a major eruptive center in the low-K western belt of the AVP. Although mineral and whole rock compositional data reflect near equilibrium crystallization of modal phenocrysts, petrogenetic modeling demonstrates that intermediate composition magmas are hybrids formed by mixing variably fractionated and contaminated mantle-derived melts and heterogeneous silicic crustal melts. Nd and Sr isotopic compositions along with trace element data indicate that silicic melts in the Washburn system are derived from deep crustal rocks broadly similar in composition to granulite facies xenoliths in the Wyoming province. Our preferred explanation for these features is that mantle-derived basaltic magma intruded repeatedly in the deep continental crust leading to fractional crystallization, silicic melt production, and homogenization of magmas, followed by ascent to shallow reservoirs and crystallization of new plagioclase-rich mineral assemblages in equilibrium with the intermediate hybrid liquids. The importance of magma mixing at Washburn volcano contrasts with recent petrogenetic models for shoshonitic magmas in the Absaroka Volcanic Province, which require a more important role for fractional crystallization. These results suggest that across-strike increases in K2O contents for rocks in the volcanic field may derive from variations in the conditions of crustal differentiation, rather than mantle processes involving a subducting slab.