The Haidewula deposit in Northwest China is a recently discovered volcanic-related uranium deposit. To determine the origin of this deposit, whole-rock geochemical, stable isotope, U–Pb isotope and trace element compositions of the pitchblende were obtained, and microthermometric analyses of the fluid inclusions were performed. The Haidewula deposit is located within the Phanerozoic volcanic basin and contains Silurian trachyte, rhyolite, rhyolitic tuff, and Triassic basalt. These Silurian volcanic rocks are characterized by high-K calc-alkaline properties and were intruded by Triassic dolerite, which served as a source for mineralization. The mineralized zones were primarily influenced by NE-NNE-trending and SE-dipping faults. Vein-like pitchblende is commonly associated with calcite, illite, quartz, pyrite, and fluorite. Geochronology indicated that uranium mineralization occurred during 235–230 Ma. The ore-forming fluids contained meteoric water with limited magmatic water and exhibited moderate to low temperatures (246–133 °C), moderate to low salinities (17.3–1.06 wt% NaCleqv) and Cl-bearing rocks. U precipitation was attributed to changes in physicochemical conditions resulting from fluid–rock interactions and fluid boiling. The uranium mineralization at Haidewula coincided with the evolution of the Tethys Ocean. During late Wenlock, an extensional environment, triggered by the closure of the Proto-Tethys Ocean, led to the extrusion of Haidewula rhyolite and trachyte. During the crustal extensional environment resulting from the subduction of the A’nyemaqen Ocean in the Middle Triassic, ore-forming fluids circulated and remobilized uranium from the Haidewula volcanic rocks. As a result of fluid–rock interactions and fluid boiling within brittle structures, the U-complexes destabilized and formed pitchblende at Haidewula.