Pb and Nd isotopic composition of granitoids from the Lake Zone, Mongolian and Gobi Altai was analyzed to decipher the continental crustal growth of heterogeneous terranes of the Central Asian orogenic belt. The granitoids were generated in the Late Neoproterozoic–Early Paleozoic juvenile crust of the Lake Zone during island-arc, accretion, and post-accretionary stages at 535–440 Ma. Their Pb and Nd isotopic characteristics are similar and illustrate the dominance of juvenile material in the source of granitoids of all three stages. An insignificant terrigenous contribution in their source provides dispersion of the Pb isotopic composition at a weak effect on the Nd isotopic composition. The Pb and Nd isotopic study of Middle Paleozoic (∼380–355 Ma) synkinematic and Late Paleozoic (∼350–270 Ma) post-kinematic granitoids in the Mongolian and Gobi Altai revealed a significant heterogeneity of their source, which is mainly inherited from terrigenous rocks of the Altai accretionary wedge variably metamorphosed under greenschist to granulite facies conditions. The main source of Altai terrigenous sediments was volcanic rocks from the Lake Zone juvenile crust with subordinate contribution of more mature rocks from the Tuva-Mongolian and Dzabkhan microcontinents, which supplied sediments with highly radiogenic Pb and Nd isotopic composition. The Pb isotopic compositions of the granitoids from the Lake Zone, Mongolian and Gobi Altai, and also the Trans-Altai Gobi (Savatenkov et al., 2016) show that their mantle source has an elevated Th/U ratio compared to the depleted mantle (Kramers and Tolstikhin, 1997). This is a hallmark of the depleted mantle source of the Paleo-Asian province. Juvenile continental crust terrains of the Central Asian orogenic belt (Lake Zone and Trans-Altai Gobi terranes) were formed in various tectonics settings. The island-arc complexes of the Lake Zone developed near the Precambrian Tuva-Mongolian and Dzabkhan microcontinents, which supplied terrigenous material with highly radiogenic Pb to granitoid sources. The Trans-Altai Gobi was a system of ensimatic island arcs separated from the Siberian paleocontinent by a continent-dipping subduction zone, which prevented the influx of ancient terrigenous material from the continent.