The Shitoukengde mafic–ultramafic intrusion is the host of the second-largest sulfide deposit after the Xiarihamu Ni-Co deposit in the East Kunlun Orogenic Belt (EKOB), northern Tibet Plateau, China. Despite several studies, the age, petrogenesis, and the cause of low Ni-tenor for this intrusion remain poorly constrained. In this study, zircons separated from the pyroxenite at Shitoukengde yield a SHRIMP U-Pb age of 418.9 ± 3.1 Ma, corresponding to the widespread magmatism of the late Silurian to early Devonian in the EKOB. Whole-rock major and trace element compositions indicate that fractional crystallization played a key role in controlling the magma composition and element distribution within the intrusion. Mafic-ultramafic rocks of the intrusion, particularly peridotite, have highly variable and exceptionally elevated (⁸⁷Sr/⁸⁶Sr)_i and negative ɛ_Nd(t) values. Some samples from the Shitoukengde intrusion exhibit initial Sr-Nd isotope ratios that overlap with those from the Xiarihamu intrusion, while others (e.g., peridotite) display higher (⁸⁷Sr/⁸⁶Sr)_i values than those observed in the latter. The unusual Sr-Nd isotopic compositions of the Shitoukengde intrusion could be attributed to the assimilation of Mg-rich carbonate within a deep-seated magma chamber. This contamination process facilitates the crystallization of olivine, consequently reducing Ni content in residual magma. Furthermore, the contamination of Mg-rich carbonate may promote oxygen fugacity and thus enhance the solubility of sulfur while restricting the sulfide saturation in the magma. We thus propose that the extensive contamination of Mg-rich carbonate is a key factor contributing to the relatively low Ni-tenor observed at Shitoukengde.