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The origins of Cenozoic granites in the Himalaya are key to understanding the evolution of the Himalayan orogen. However, it is unclear whether these granites represent primary melts, and the nature of their magma source is controversial. Here, we present a systematic element and Sr–Nd–B–Mo isotope study of Cenozoic granites from the Yardoi area in the eastern Tethyan Himalaya, China. These granites can be divided into two groups: mid‐Eocene porphyritic two‐mica granites with low SiO2 contents (65.9−69.6 wt.%) and adakitic geochemical signatures, and mid‐Eocene to Miocene equigranular granites with high SiO2 contents (71.6−75.5 wt.%). The high‐SiO2 granites (HSG) have similar Sr−Nd isotope compositions to the low‐SiO2 granites (LSG), but they have distinct δ11B values of −19.4‰ to −11.4‰ and −10.6‰ to −6.89‰. This indicates that the two groups have different sources, with the LSG derived by partial melting dominantly of metamafic rocks at thickened lower crustal conditions, and the HSG generated by partial melting of the mid‐crust metasedimentary rocks with less enriched Nd isotope compositions. The δ98/95Mo of the LSG and HSG are highly variable with values of −0.68‰ to 0.12‰ and −1.13‰ to 0.46‰, respectively. δ11B values of the HSG correlate positively with δ98/95Mo and Sr/Y values and correlate negatively with K2O, Rb, Zr, and Rb/Sr, reflecting the addition of external metamorphic fluids during anatexis of the metapelites. The B–Mo isotope data robustly suggest source‐controlled compositional diversity of the Himalayan granites, which could provide clues to the physical and geochemical responses during the evolution of a large orogen.