The evolution characteristics of hydrothermal activity and superimposed uranium mineralization in the Qianjiadian ore field in southwestern Songliao Basin are still controversial and lack direct evidence. In this comprehensive study, a detailed identification of dolerite and hydrothermally altered un-mineralized sandstone and sandstone-hosted ore in the Yaojia Formation have been performed through the use of scanning electron microscopy observation, electron probe, carbon-oxygen-sulfur isotope, and fluid inclusion analyses. The results show that the hydrothermal fluid derived from the intermediate-basic magma intrusion is a low-temperature reducing alkaline fluid and rich in CO2, Si, Zr, Ti, Fe, Mg, Mn, and Ca, producing different types of altered mineral assemblages in the rocks, including carbonation, pyritization, sphalerite mineralization, clausthalite mineralization, silicification, and biotitization. Specifically, the carbonate minerals in sandstone are mixed products of deep hydrothermal fluid and meteoric water, with carbon and oxygen isotopes ranging from −5.2‰ to −1.7‰ and −20.4‰ to −11.1‰, respectively. Carbon source of the carbonate minerals in dolerite is mainly inorganic carbon produced at the late stage of intermediate-basic magma evolution, with carbon and oxygen isotopes from −16.1‰ to −7.2‰ and −18.2‰ to −14.5‰, respectively. Various carbonate minerals in the rocks may have been precipitated by the hydrothermal fluid after the magmatic stage, due to the change of its CO2 fugacity, temperature, and cation concentration during the long-term evolution stage. A series of carbonate minerals were generated as calcite, dolomite, ankerite, ferromanganese dolomite, and dawsonite. The precipitation processes and different types of carbonate mineral mixtures identified in this study mainly occur as parallel, gradual transition, interlacing, or inclusion metasomatism in the same vein body, without obvious mineralogical and petrologic characteristics of penetrating relationship. Homogenization temperature of fluid inclusions in calcite is high, in the range of 203–234 °C, with a low salinity of 0.71–4.34% NaCl, and the data range is relatively concentrated. Homogenization temperature of fluid inclusions in ankerite is usually low, ranging from 100 °C to 232 °C, with a high salinity of 4.18–9.98% NaCl. The precipitation processes of carbonate minerals and the results of this study are basically in consistent. Overall, the sandstone-type uranium deposits have a temporal and genetic relationship with hydrothermal activities during Paleogene. (1) Hydrothermal activity was directly involved in uranium mineralization, result in dissolution and reprecipitation of earlier uranium minerals, forming uranium-bearing ankerite and complexes containing uranium, zirconium, silicon, and titanium. (2) Hydrothermal fluid activity provided reducing agent to promote hydrocarbon generation from pyrolysis of carbonaceous fragments and accelerate uranium precipitation rate. (3) Regional water stagnation prolongs reaction time, contributing to huge uranium enrichment. This study provides new petrologic, mineralogical, and geochemical evidence for multi-fluid coupled and superimposed mineralization of sandstone-hosted uranium deposits in the sedimentary basin.