The Nagengkangqie'er (Nageng) silver deposit, situated in the Eastern Kunlun Orogenic Belt (EKOB), Northwestern China. It contains 5,070 tons of contained silver at a silver grade of 325 g/t. Nonetheless, the genesis of the Nageng silver deposit is still under debate, due to the absence of definitive constraints the mineralization age and the metal sources. The U-Pb data analysis of a post-ore calcite vein established the minimum age of the mineralization at 207 ± 3 Ma, whereas the maximum age of 217 ± 4 Ma was determined from zircon U-Pb data obtained from the altered and mineralized rhyolitic porphyry host-rock. These temporal limitations suggest that the mineralization formed at ca. 217–207 Ma, and it is associated with the post-collisional setting of the Paleo-Tethys evolution in the EKOB. The distinct textural patterns, as revealed by petrographic observations, suggest three types of pyrites: py1 is composed of euhedral pyrite in the early barren quartz vein at stage 1, py2 is represented by subhedral-anhedral grains in massive ore veins at stage 2, and py3 forms euhedral crystals of varying sizes, which are interspersed with early-formed marcasite in the quartz + calcite + silver-bearing sulfosalt-dominated veins at stage 3. In-situ δ34S values of pyrites range between −2.33 ‰ and −0.37 ‰, indicating a dominantly magmatic origin. EPMA studies have revealed that silver in the Nageng deposit predominantly occurs as silver-bearing galena at stage 2, whereas silver is enriched in sulfosalts of stage 3. From py1 to py3, a decrease in the Co-content indicates a decrease in the ore-forming fluid temperatures. The presence of stage 3 sulfide, sliver-bearing sulfosalt, and calcite-quartz in a fracture-filled vein indicates low-pressure conditions during its formation, compared to stages 1 and 2. In summary, the Nageng deposit is a typical magmatic-hydrothermal vein-type Ag-Pb-Zn deposit. Fluid cooling and decrease in pressure, coupled with decreases in fO2 and fS2, are the parameters inferred to have led to a decrease of silver solubility in the hydrothermal fluids and, successively, promoted extensive Ag deposition.