The subduction and demise of an ocean plate are generally recognized as essential processes that result in the reworking and maturation of the continental crust. The northern Lhasa Terrane in central Tibet represents the forefront of the Lhasa-Qiangtang collision belt following the closure of the Bangong-Nujiang Ocean. Thus, it is a pivotal location to study the transition processes from oceanic lithosphere subduction to continental collision as well as pertinent crustal growth mechanisms. Here, we present zircon U-Pb dating, whole-rock major and trace element and Sr-Nd isotope, and zircon Hf isotope and trace element data of the Mendang igneous complex, Baingoin County, northern Lhasa Terrane. Geochronological results show that the granodiorites, trachydacites, and rhyolites in the Mendang igneous complex formed at ca. 122−116 Ma, 97 Ma, and 73 Ma, respectively. The Early Cretaceous granodiorite samples are peraluminous with high SiO2, Al2O3, and K2O contents, and moderate A/CNK (molar ratio of Al2O3/[CaO + Na2O + K2O]) values, which are similar to those of typical felsic peraluminous I-type granites. The granodiorites are characterized by enrichment in light rare earth elements and large ion lithophile elements (e.g., Rb) and depletion in high field strength elements (e.g., Nb, Ta). They also show the most enriched whole-rock Sr-Nd [(87Sr/86Sr)i = 0.7072−0.7078; εNd(t) = −7.60 to −5.08] and zircon Hf [εHf(t) = −4.46 to +1.02] isotope compositions, indicating that the Early Cretaceous granodiorites were likely derived from an ancient basement under a subduction setting. The trachydacites have uniform SiO2, high Al2O3, Sr contents, and Sr/Y values, and low Y and Yb contents, belonging to adakitic rocks. They show more depleted whole-rock Sr-Nd [(87Sr/86Sr)i = 0.7065−0.7066; εNd(t) = −0.56 to −0.22] and zircon Hf [εHf(t) = 4.36−7.84] isotopes than the granodiorites, suggesting that the trachydacites may have generated from partial melting of the juvenile thickened lower continental crust. The rhyolites have the highest SiO2 and K2O contents in the Mendang igneous complex, and significant depletion of Ba, Sr, Eu, P, and Ti. They have slighter more enriched whole-rock Nd [εNd(t) = −3.71 to −1.16] and zircon Hf [εHf(t) = 1.03−4.31] isotope compositions than the trachydacites. These features suggest that the rhyolites were highly fractionated products of the crustal melts. Whole-rock Sr-Nd and zircon Hf isotopes of the Mendang igneous complex show a kink trend from enrichment to depletion and then transfer to enrichment again, signifying an increased contribution of juvenile materials in the northern Lhasa Terrane toward progressively replacing the ancient lower crust and accumulating to newly formed crust. The estimated crustal thickness beneath the northern Lhasa Terrane shows a sharp increase from the Early to Late Cretaceous and peak at ca. 97 Ma, whereas it largely decreases in the Late Cretaceous. Integrated with previous studies, we propose that the formation of the Mendang igneous complex (122−73 Ma) elaborately documents the regional tectonic transition from oceanic lithosphere subduction to demise as well as continental crustal differentiation and maturation. The rollback and breakoff of the southward subducted Bangong-Nujiang oceanic slab in the Early Cretaceous initiated diverse magmatism in the northern Lhasa Terrane. During the early Late Cretaceous, the widespread adakitic and Mg-rich magmatism was attributed to the delamination of the thickened lithosphere following the final amalgamation of the Lhasa and Qiangtang Terranes. In the late Late Cretaceous, post-collisional extension induced the formation of the rhyolites in the northern Lhasa Terrane. The growth and destruction of the continental crust had certain tempos from the oceanic lithosphere subduction to continental post-collision stage.