Within the Himalayan collisional belt, granites occur along two subparallel belts, namely, the Tethyan Himalayan Sequence (THS) and the Greater Himalayan Crystalline Complex (GHC). In this study, Eocene adakitic rocks and leucogranite are found only in the northern Himalayas, so further research is required to constrain their origin. Here, we present zircon U–Pb and monazite U–Th–Pb ages, Sr–Nd–Pb and Hf isotopes, and whole-rock major and trace elements for Liemai muscovite granite in the eastern Himalayan region. The U–(Th)–Pb results show that Liemai muscovite granite was emplaced at 43 Ma, and that its geochemical characteristics are similar to those of adakitic rocks of the same age (Dala, Quedang, Ridang, etc.). Combined with previous studies, both Eocene adakitic rocks and leucogranite are high-potassium calc-alkaline peraluminous granites. The former is relatively rich in large-ion lithophile elements (LILEs), such as Ba and Sr, and relatively deficient in high-field-strength elements (HFSEs), such as Nb, Ta, Zr, and Y, with weak or no Eu anomalies, and the average light rare earth element (LREE)/heavy rare earth element (HREE) ratio is 17.8. The latter is enriched in LILEs (such as Rb) and U, Ta, and Pb, and depleted in HFSEs (such as Nb and Zr), La, and Nd, with obvious negative Sr, Ba, and Eu anomalies and a mean LREE/HREE ratio of 10.7. The 87Sr/86Sr of the former is in the range of 0.707517–0.725100, εNd (t) ranged from −1.2 to −14.7, the average is −11.6, εHf (t) ranged from −0.5 to −65, the average is −12.2. The average values of (206Pb/204Pb) i, (207Pb/204Pb) i and (208Pb/204Pb) i are 18.788, 15.712 and 39.221, respectively; The 87Sr/86Sr of the latter is in the range of 0.711049~0.720429, εNd (t) ranged from −9.8 to −13.8, the average is −12.3, εHf (t) ranged from −4.2 to −10, the average is −6.7. The isotopic characteristics indicate that adakitic rocks and leucogranites are derived from the ancient lower crust, and both may be derived from metamorphic rocks of the GHC. In this paper, the origin of the two is associated with the transformation of the Himalayan tectonic system during the Eocene, and it is inferred that the deep crust may have altered the tectonic environment (temperature and pressure), resulting in an obvious episodic growth trend of leucogranite and significant development of adakitic rocks from 51 to 40 Ma. From 40 to 35 Ma, the development of Eocene magmatic rocks was hindered, and adakitic rocks disappeared. It is proposed that the genetic difference is related to the transition from high to low angles of the subducting plate in the crustal thickening process.