Elemental chemistry, radiogenic isotopic data, and zircon U-Pb inheritance patterns for the Famatinian-Puna arc suggest that the primary petrogenetic process operating in the arc was mixing between subarc mantle-derived gabbroic magmas and metasedimentary materials without a substantial component of lower-crustal continental basement rocks. This mixing is observable in the field and evident in variations of chemical elemental parameters and isotopic ratios, revealing that hybridization coupled with fractionation of magmas took place in the upper 25 km of the crust. Intermediate and silicic plutonic rocks of the Famatinia-Puna arc formed in a subduction setting where the thermal and material input of mantle-derived magmas promoted fusion of fertile metasedimentary rocks and favored mixing of gabbroic and dioritic magmas with crustal granitic melts. Whole-rock geochemical and isotopic data for the Famatinian-Puna magmatic belt as a whole demonstrate that the petrologic model studied in detail in the Sierra Valle Fértil-La Huerta section has the potential to explain generation of plutonic and volcanic rocks across the Early Ordovician western Gondwanan proto-Pacific margin. This example further underscores the significance of passive-margin sedimentary accumulations in generating continental arcs.