Many magmatic Ni-Cu sulfide deposits have been found to be associated with Permian basaltic magmatism in the Central Asian orogenic belt, Xinjiang, China. The style of basaltic magmatism and the origin of associated Ni-Cu sulfide deposits in the region are highly debated. The Huangshandong mafic-ultramafic intrusion is at the center of the debate mainly because it hosts the largest magmatic Ni-Cu sulfide deposit in the region. In this paper we report integrated petrological and geochemical data for the Huangshandong Ni-Cu sulfide deposit. The host intrusion consists of a massive gabbronorite unit and a layered sequence, which is composed of two to three ultramafic layers overlain by gabbroic rocks with visible modal layering. Important sulfide mineralization in the intrusion is associated with the ultramafic rocks and massive gabbronorite. The ultramafic rocks and massive gabbronorite are characterized by moderate enrichments in light rare earth elements (LREE), pronounced negative Nb-Ta anomalies relative to Th and La, positive ɛNd (t = 274 Ma) values (6.6–8.3), low initial 87Sr/86Sr ratios (0.7031–0.7038), low initial 206Pb/204Pb ratios (17.7–18), and positive ɛHf values of zircon (14–17). These data are consistent with mixing between a depleted mantle-derived magma and a granitic melt formed by partial melting of a juvenile arc crust as a result of mafic magma underplating. Olivine crystals enclosed in large clinopyroxene and plagioclase crystals from the ultramafic rocks have Fo contents up to 83 mol %. The contents of Ni in the olivine crystals decrease rapidly with Fo contents, indicating sulfide segregation from magma during olivine crystallization. Numerical modeling using bulk sulfide compositions and constraints from olivine-liquid relationships reveals that the parental magma of the intrusion was significantly depleted in PGE and contained <7 wt % MgO. Depletion of PGE in the magma can be explained by previous sulfide segregation possibly due to magma mixing in a staging chamber. Fractional crystallization and addition of external sulfides from juvenile arc crust appear to have played a critical role in triggering the second event of sulfide segregation to form the deposit. We believe that the Huangshandong sulfide ore-bearing intrusion formed by basaltic magmatism related to postsubduction delamination and asthenosphere upwelling instead of a deep-seated mantle plume.