The eastern Tianshan orogenic belt, northwestern China, hosts ~120 mafic-ultramafic intrusions and at least six of them host significant Ni-Cu sulfide mineralization of which the Permian Huangshandong intrusion is the largest. The mafic-ultramafic rocks of the Huangshandong intrusion comprise lherzolite, gabbronorite, gabbro, and diorite. Individual orebodies are composed of pyrrhotite, pentlandite, and chalcopyrite as disseminated to net-textured or massive to semimassive sulfide mineralization. Oxide-bearing sulfide mineralization contains 1 to 5% magmatic magnetite that has ilmenite and spinel exsolution lamellae. Silicate rocks and sulfide mineralization have variable whole-rock platinum group elements (PGE; 0.38−362 ppb), Cu (42−97,000 ppm), and Ni (26−33,000 ppm) concentrations. The mineralization is broken out into two types termed oxide rich and oxide poor. The oxide-rich sulfide mineralization has high PGE concentrations with low 187Re/188Os ratios (38.9−151), whereas oxide-poor sulfide mineralization has low PGE concentrations with high 187Re/188Os (159−781). Both oxide-rich and -poor sulfide mineralization have highly variable γOs values (49−189 and 30−278, respectively). Oxide-rich sulfide mineralization contains magnetite with variable amounts of MgO, TiO2, Al2O3, FeOtotal, Cr, V, Zn, and Sn, indicating that they crystallized from different stages during magma differentiation. We propose that the host intrusion and associated sulfide mineralization were derived from high Mg basaltic magmas from a mantle source that was previously modified by subducted oceanic slab. Oxide-poor sulfide mineralization of the Huangshandong intrusion formed from a magma that underwent <0.03% sulfide removal before emplacement and was thus PGE depleted. Oxide-rich sulfide mineralization formed from magma that had much lower amounts of sulfide (<0.003%) removed in the early stage before entering the Huangshandong magma chamber. An early sulfide saturation event was likely associated with fractionation of silicate minerals in a deep-staging magma chamber. The second sulfide saturation event that formed the sulfide mineralization was probably triggered by selective crustal contamination and fractionation in the high-level chamber where mixing of magmas and accumulation of immiscible sulfide occurred.