This is a synthesis of published and new data on the Kalba batholith in Eastern Kazakhstan, the large granitic body in the western part of the Central Asian Orogenic Belt. The batholith consists of granodiorite-granite and leucogranite rocks discriminated on the basis of major- and trace-element chemistry and isotope systematics. The granodiorite-granite rocks, which form the bulk of the batholith, are compositionally variable and can be classified as mixed S-I-type granites. The leucogranites occurring as a few large intrusions in the northwestern part of the batholith have more stable compositions, with high contents of REE, HFSE, F, Li, and B, typical of A-granites. Judging by the isotope systematics of the Kalba granites, compared with that of their potential parent rocks from the Kalba-Narym zone and its surroundings, the two groups originated by different mechanisms in two magmatic events. The granodiorite-granites were produced by large-scale melting of crustal material, including the metabasaltic basement and overlying metavolcanic and metasedimentary rocks. The origin of leucogranites was associated with low-degree partial melting of the deepest Kalba-Narym sediments under the effect of fluoride fluids. The batholith formation spanned about 21 myr: granodiorites and granites formed in the 297–286 Ma interval and leucogranites between 288 and 276 Ma. The ages of the two events bracket the intraplate postorogenic stage of the CAOB history that was coeval to the formation of the Tarim large igneous province.