Porphyry-related Cordilleran polymetallic mineralization in the Morococha district, central Peru, displays a deposit-scale base metal zonation, a common feature observed in many ore deposits of this type. The distinct pattern of zonation consists of Cu-rich ores in the core area and increasingly Zn-, Pb-, and Ag-rich ores in more distal veins and replacement orebodies. We investigated the changing composition of key ore minerals throughout these zones. They are important indicators for the conditions of mineral precipitation and evolving hydrothermal fluid. The mineral species stannoidite Cu8(Fe,Zn)3Sn2S12, vinciennite Cu10Fe4Sn(As,Sb)S16, and tennantite-tetrahedrite have variable Cu content and Fe2+/Fe3+ values between the different base metal zones. Controlled by coupled substitution mechanisms, they show Cu-excess and predominantly ferric Fe compositions in the central areas (Cu and Zn-Cu zones), whereas stoichiometric Cu values and mixed Fe3+ and Fe2+ compositions are typical in the more distal zones (Zn-Pb-Ag and Ag-Pb). These compositional changes are interpreted to reflect decreasing oxidation state of the cooling and evolving fluid and increasing reaction with the host rock toward outer parts of the deposits. Initially high Cu, Fe, and S values in the fluid decrease with precipitation of Cu- and Fe-sulfides. As result of decreasing oxidation state and Fe and Cu values in the fluid, Fe in tennantite-tetrahedrite is increasingly substituted by competing Zn, and Cu by Ag. These data show that compositions of major and even minor ore-forming minerals reflect metal content, oxidation and sulfidation state, and degree of buffering of an evolving hydrothermal fluid by the host rock on a district-scale.