Early Paleozoic boninites occur in the Central Qilian orogenic belt, Northwest China. Their petrogenesis provides insights into lithosphere process and tectonic evolution of the Qilian block. In this paper, we carry out a study of geochronological, geochemical and Sr-Nd isotopic compositions for the Early Paleozoic boninites in the Lajishan area of the Central Qilian block. The Lajishan boninites (∼483 Ma) have high Al2O3/TiO2 (36.7–64.7) and CaO/TiO2 (31.1–49.6) ratios, and high MgO (7.86–10.47 wt%), Cr (439–599 ppm) and Ni (104–130 ppm) contents, indicating that the boninites result from a refractory mantle source. They are depleted in high field-strength elements (HFSE) and enriched in large ion lithophile elements (LILE), coupled with slightly high initial 87Sr/86Sr values of 0.7059–0.7074 and low eNd(t) values of −1.05 to +2.66, indicating that the mantle source was metasomatized by subducted slab-derived components. We found that an assemblage of low-Ca group and high-Ca group boninites occurred in the Lajishan belt. The high-Ca group boninites were derived from relatively fertile mantle with slightly higher melting degree, whereas the low-Ca group boninites were generated by partial melting of more refractory mantle wedge peridotites with slightly lower melting degree. The assemblage of low-Ca group and high-Ca group boninites reveals that the low-Ca group boninites were generated by the further melting of the more refractory mantle source after the segregation of the high-Ca group boninitic magmas in response to the back-arc basin opening. In the light of reported boninites worldwide, a diagram of Zr/Y vs. CaO/Al2O3 is used to identify boninites in fore-arc and back-arc regions. We suggest that the Lajishan boninites represent the products of back-arc basin development in response to the northward subduction of the Qaidam-West Qinling ocean slab.