The Qumushan (QMS) syn-collisional granodiorite, which is located in the eastern section of the North Qilian Orogen at the northern margin of the Greater Tibetan Plateau, has typical adakitic characteristics and also contains abundant mafic magmatic enclaves (MMEs). This recognition offers an unprecedented insight into the petrogenesis of both the adakitic host granodiorite and the enclosed MMEs. The MMEs and their host granodiorites share many characteristics in common, including identical crystallization age (~430Ma), same mineralogy, similar mineral chemistry and whole-rock isotopic compositions, indicating their genetic link. The MMEs are most consistent with being of cumulate origin formed at earlier stages of the same magmatic system that produced the QMS adakitic granodiorite. Subsequent replenishment of adakitic magmas could have disturbed the cumulate piles as “MMEs” dispersed in the adakitic granodiorite host during emplacement. The geochemical data and petrogenetic modeling of trace elements suggest that the QMS adakitic host granodiorite is most consistent with fractional crystallization dominated by the mineral assemblage of the MMEs. The parental magma for the QMS granodiorite is best explained as resulting from partial melting of the ocean crust together with recycled terrigenous sediments during continental collision, which may have also experienced interaction with mantle peridotite during ascent.