—We present results of geochemical and isotope (Rb–Sr, Sm–Nd, and Lu–Hf) studies of the early Paleozoic plagiogranitoid associations in the south of the Lake Zone in Western Mongolia, which formed at the island-arc and accretion–collision stages of the regional evolution. According to the petrogeochemical composition, the early Paleozoic plagiogranitoid associations of the island-arc (Tugrug, Hatan-Hunga, Udzur-Hunga, and Bayasgalant plutons, 531–517 Ma) and accretion–collision (Tugrug, Mandalt, and Dut Uul plutons, 504–481 Ma) stages are high- and low-alumina rocks. The recognized types of plagiogranitoids, with regard to their trace-element composition, indicate that their parental melts were generated from MORB-type metabasites at ≥10–12 kbar, in equilibrium with garnet-containing restite, and at ≤8 kbar, in equilibrium with plagioclase-containing restite. The Sr–Nd isotope data on the rocks and the Lu–Hf isotope parameters of their magmatic zircons show two groups of plagiogranitoids, with different sources of melts. The first group includes plagiogranitoid associations of most plutons (Tugrug, Udzur-Hunga, Hatan-Hunga, Bayasgalant, and Dut Uul) with isotope parameters (εNd = 8.5–4.6, (87Sr/86Sr)0 = 0.7034–0.7036, and εHf = 14.7–11.9) indicating the juvenile nature of their sources. The second group includes plagiogranitoids of the Mandalt pluton; their isotope parameters (εNd = 1.4–0.2, (87Sr/86Sr)0 = 0.7053, and εHf = 7.2–5.4) indicate that the parental melts were generated mostly from enriched-mantle metabasites. The Hf isotope data on inherited and xenogenic zircons (664–519 Ma) from the early Paleozoic plagiogranitoid associations of the southern Lake Zone permit us to separate these rocks into three groups according to their εHf values (14.5–12.8, 2.9, and 10.6–6.7). The Hf isotope parameters of magmatic and inherited zircons, with regard to their age, indicate that the source of the parental melts lacked rocks with a long crustal history, such as the early Precambrian associations of the Dzavhan microcontinent.