The Macusani Volcanics and related rocks (SE Peru) are well known examples of erupted strongly peraluminous rare-metal rich silicic magmas. We used the phenocryst/matrix glass method to determine relevant mineral/melt partition coefficients to facilitate modeling of such systems. Concentrations of trace (Li, Be, B, Al, P, Ti, Mn, Zn, Ge, Rb, Sr, Zr, Nb, Sn, Cs, Ba, La, Sm, Eu, Gd, Yb, Ta, W, Pb and U) and major elements were measured in obsidians, matrix glasses, glass inclusions, phenocrysts and phases from biotite reaction zones by Laser-Ablation ICP-MS and Electron Microprobe Analysis. The derived phenocryst/melt partition coefficients for quartz, plagioclase, sanidine, biotite, muscovite, andalusite and ilmenite are compared with values from reference silicic magmas and literature. Mineral/biotite partition coefficients are calculated for tourmaline and hercynite. The database is then applied to model chemical fractionation in Macusani magmas. Fractional crystallization and partial melting trends (with the B concentration used as a proxy for the fraction of residual liquid) generate progressively more evolved (higher Rb, Nb, Sn, Cs and Ta and lower Sr, Ba and Pb) residual liquids. The trace element concentrations in obsidians are reproduced for 50-70% crystallization of matrix glasses from ash-flow tuffs. This demonstrates that differentiation of magmas parental to the ash-flow tuffs can generate the highly evolved obsidian-forming liquids. Based on this, we present an updated model for crustal melting and the generation of the Macusani magmas. A metapelitic component dominates the source region but calcic plagioclase cores enriched in Sr, Ba and La suggest an affiliation with mafic magmas, which were likely potassic to ultrapotassic. The presence of a mafic component is consistent with the high heat fluxes in the source region and accounts for specific magmatic variables (i.e., middle crustal anatectic zone, very reducing fO2, high F). Petrogenetic processes differ significantly between Macusani Volcanics suites and two-mica leucogranites despite both having nearly identical source rocks, mineral assemblages and compositions.