Collision-related magmatism in accretionary-to-collisional orogens records a tectonic transition from early subduction-accretionary processes to collisional orogenesis, and also plays a significant role in continental growth. Here, we present an integrated study of field observations, geochemistry, whole-rock Rb-Sr and Sm-Nd isotopes, and zircon U-Pb ages and Lu-Hf isotopes for the Laohushan mafic to felsic magmatic rocks related to initial collision between the Alxa terrane and the Central Qilian block along the North Qilian orogenic belt, northeastern Tibet. The Laohushan magmatic rocks are dominated by quartz diorites (ca. 426 Ma), with minor tonalites enclosing dioritic enclaves (ca. 430 Ma) and hornblendite xenoliths (ca. 448 Ma), and some coeval dolerite dikes (ca. 427 Ma) intruded into the accretionary complex. The quartz diorites are characterized by light rare earth element (LREE)- and large ion lithophile element (LILE)-enrichment but have high field strength element (HFSE)-depleted trace element patterns and negative initial εNd (–1.6 to –2.9) and positive zircon initial εHf (+3.0 to +6.2) values. The dioritic enclaves are also characterized by LREE-enriched and HFSE-depleted patterns and have mostly negative initial εNd (–9.2 to +0.03) but positive zircon initial εHf (+3.0 to +5.9) values. These geochemical and isotopic features, together with isotopic mixing calculations, suggest that the quartz diorites were likely derived from partial melting of the lower crust dominated by accreted mafic oceanic rocks with minor sediments, whereas the dioritic enclaves originated from underplated mantle-derived magmas mixed with crust-derived melts. The hornblendite xenoliths have high MgO, Cr, and Ni contents, positive Th, U, and Pb anomalies, and negative Nb, Ta, and Ti anomalies. They have negative initial εNd (–2.8), near chondritic zircon initial εHf (–0.4 to +1.4) values and an Archean Nd model age (TDM = 2.74 Ga), suggesting that the hornblendites were likely produced by partial melting of subcontinental lithospheric mantle peridotite that was metasomatized by subduction-related melts beneath the Archean–Proterozoic Alxa terrane. We propose that partial melting of the lower crust of the early Paleozoic North Qilian orogenic belt was in response to slab breakoff and asthenospheric upwelling during the initial stage of collisional orogenesis. This study demonstrates that heterogeneous magma sources, involving accretionary materials (i.e., accreted oceanic crust and sediments) and various mantle-derived components, were mixed to form the collision-related magmatic rocks. It also highlights the significance of collision-related magmatism in continental growth and stabilization of newly-assembled crust in accretionary-to-collisional orogens.