Permian-Triassic mafic-ultramafic intrusions in the Central Asian orogenic belt host a number of magmatic Ni-Cu sulfide deposits, containing a total of 3.6 million tonnes (Mt) Ni, with the Ni grades ranging from 0.4 to 2.3 wt % in different deposits, making the belt an important Ni producer after the Jinchuan Ni-Cu sulfide deposit in China, the third largest one in the world. The Hongqiling No. 7, Piaohechuan No. 4, and Kalatongke intrusions are three major hosts of economically important deposits in the belt. Sulfide saturation of mantle-derived mafic magma is key to the formation of magmatic Ni-Cu sulfide deposits. In order to examine the sulfur source and the trigger for sulfide saturation of these intrusions, we present a study based on in situ S isotope analyses for sulfides in sulfide ores and country rocks, whole-rock C isotope analyses for sulfide ores and country rocks of these intrusions, and whole-rock S and Re-Os isotope analyses for country rocks of these intrusions. The sulfides in sulfide ores have restricted δ34S of –1.0 to 1.1‰, similar to the δ34S of mid-ocean ridge basalt (MORB)-type mantle (–1.5 to 0.6‰), whereas the sulfides in different country rocks have average δ34S varying from –17.6 to –6.5‰, much lower than those for the sulfides in sulfide ores. The remarkably different δ34S of the sulfides in sulfide ores and country rocks does not support the significant addition of external crustal sulfur to the magmas. On the other hand, the sulfide ores of the three intrusions have restricted δ13C of –26.7 to –24.1‰, similar to those of the country rocks. Permian gneiss, slate, and tuff in the Hongqiling-Piaohechuan area have δ13C ranging from –26.7 to –21.3‰, and the Carboniferous muddy slate of the Nanmingshui Formation near the Kalatongke intrusion has δ13C of –24.7‰. These values are consistent with the δ13C of organic carbon in the crust (–28 to –20‰) but apparently lower than the δ13C of MORB (–7 to –5‰). Modeling results indicate that about 1-km3-volume mantle-derived mafic magma could contain enough sulfur to account for the mass of sulfides in the three intrusions. The trigger for the sulfide saturation of the mafic magma is likely related to the reduction of relatively oxidized magma with the addition of organic-rich crustal components. Crustal Os from the organic-rich crustal components may also lead to the elevated γOs(t) (30–300) for the sulfide ores of these three intrusions, which is decoupled with the MORB-type mantle δ34S of the sulfides in sulfide ores. Our study indicates that the addition of external crustal sulfur may not be necessary to trigger the sulfide saturation of small Ni-Cu sulfide deposits, such as those in the Central Asian orogenic belt.