The Himalayan orogen preserves multi-episodes of pre-Cenozoic magmatic history, but remains a subject of debate for their tectonic settings, limiting a better understanding of the Himalaya litho-tectonic structure. This study demonstrates the protolith nature of granitic gneisses and garnet amphibolites collected from three areas (Kangmar, Cona, and Arun Valley) in the east-central Himalaya. Then we investigated the bulk-rock major and trace elements, Sr-Nd isotopes, zircon U-Pb ages, and Hf isotopes. The garnet amphibolites are classified into sub-alkaline basalt and show tholeiite affinity. Garnet amphibolites from the Kangmar and Cona areas show Paleozoic (512–450 Ma) and Neoproterozoic (803 ± 8 Ma) protolith ages, respectively. Geochemically, they display similar MORB-like trace element features and enrich in large ion lithophile elements (LILEs: Rb, Th, U, Sr, Pb) and Ta, Ti, and mantle-like Sr-Nd isotopes with initial 87Sr/86Sr of 0.667787–0.705088 and εNd(t) of 2.9–5.0. The high Th/Yb and Ba/Th ratios and varied εHf(t) (−22.3–11.0) indicate subduction-related material contributions. The geochemical affinity to MORB and slab contributions is associated with a back-arc basin setting. Besides, garnet amphibolites from Arun Valley yield a protolith age of 1869 ± 10 Ma and are divided into two groups. Group I exhibits enriched LREE patterns [(La/Yb)N = 5.99–6.44] and shows wide εNd(t) of −1.3 to 7.1, variable Th/Ta and Nb/La, and high Zr/Y ratios. These features suggest the protolith of Group I might be continental flood basalts. In comparison, Group II exhibits MORB-like REE patterns, enrichments of LILEs, and depletions of high field strength elements (HFSEs) similar to island arc basalt. Thus, the geochemical affinity to MORB and arc-like features indicates they are metamorphosed from back-arc basalts. As for the granitic gneisses, the Kangmar and Cona samples give a Paleozoic age range of 552–438 Ma, due to a protracted (∼110 Myr) magmatism. The Kangmar granitic gneisses were metamorphosed from arc-related I-type granites, by contrast, the Cona granitic gneisses belong to A-type granites formed in a back-arc setting. These Paleozoic granitic gneisses show similar εHf(t) of −7.1–−2.5 and TDM2 of 1229–1923 Ma, indicating they were derived from partial melting of Meso- to Paleoproterozoic crust. Furthermore, the Arun Valley granitic gneisses give an 1819 ± 6 Ma protolith age and show arc features with enriched LILEs and depleted HFSEs. The wide εHf(t) of −5.3–13.2 indicates the varying degree of mantle contributions resulting from slab break-off or roll-back. Therefore, the Himalaya witnessed bimodal magmatism during Paleoproterozoic, Neoproterozoic, and Paleozoic related to Andean-type orogeny. The multi-episodes of Andean-type magmatism contribute to the formation of the Cenozoic Himalayan architecture.