The petrogenesis of late Ordovician–early Silurian adakitic plutons in the North Qilian suture zone (NQSZ) and their copper mineralization potential remain poorly understood. Here we present a detailed study of the Heishishan (HSS) granodiorite–granite pluton, spatially associated with Cu–Au mineralization in the eastern section of the NQSZ. Zircon U–Pb dating confirms that the granodiorite–granite were formed at ca. 438–435 Ma, in association with a continental collision. Geochemically, the granitoids resemble low-Mg adakitic rocks featured by elevated Sr/Y and (La/Yb)N ratios with depleted MgO, Cr, and Ni concentrations, suggesting minimal mantle contribution. They are sodium rich with K2O/Na2O < 1, and have higher and more varied Sr/Y, but lower La/Yb than those from the continental lower crust. The εHf(t) values of zircon grains are positive and vary in a wide range of +2.0–12.7, indicating a heterogeneous source rather than a single arc basaltic source. They show moderately radiogenic Sr and Nd isotope compositions with initial 87Sr/86Sr ratios of 0.705101–0.706312 and εNd(t) values of +0.5–1.0, most likely a mixed source of the oceanic basaltic crust plus ca. 15–20% overlying sediments. The magmatic oxygen fugacity was relatively low as indicated by zircon Ce(IV)/Ce(III) ratios of 32–156, which is unfavorable for a large copper mineralization.