Multistage magmatic thermal events occurred in the Yardoi Dome and contain important information on the tectonomagmatic processes. The dome has played a crucial role in understanding the collisional evolution of the Tethyan Himalayan. We present new geochronological and geochemical data for muscovite-granite exposed in the Liemai area, Eastern Tethyan Himalayan Belt. Liemai muscovite-granite is strongly peraluminous, with A/CNK values characterized by evolved geochemical composition with high contents of SiO2-enriched large-ion lithophile elements, and is depleted of high-field-strength elements. These geochemical features indicate that granites possibly derived from partial melting of metasedimentary rocks and plagioclase fractional crystallization probably played a critical role in production of peraluminous granitic melts. Zircon U–Pb dating from muscovite-granite yielded ages of approximately 48.5 ± 1.1 Ma, representing its crystallization ages. This age is the oldest age of Tethyan Himalayan leucogranite from the Yardoi Dome and adjacent areas. However, the inherited zircon cores have ages of 135.7–3339.2 Ma. The εHf(t) values of all zircons vary from –6.4 to –2.3 and have varying Hf-isotope crustal model ages of 731–839 Ma. The geochemical and isotopic compositions indicate that magma of the Liemai granite can most likely be interpreted as products of the break-off related to thermal perturbation along the break-off window associated with the subduction of Neo-Tethyan slab. These magmas were derived mainly from the anatexis of ancient crustal materials under contraction and thickening conditions due to subduction of the Indian continent beneath southeastern Tibet.