Dating the activity of complex faults and fracture systems is crucial for creating reliable geological models for various tectonics and subsurface engineering applications. This study presents a comprehensive study integrating U–Pb fracture cement dating, trace elements, and fluid inclusion temperature analysis with seismic analysis of faults, fault diagenesis, and burial history studies to better constrain faulting and fracture activities in an intra-cratonic strike-slip fault system in the northern Tarim Basin. Seismic profiles indicate at least three distinct phases of fault activity corresponding to the Middle Ordovician, Permian, and Paleogene periods. Fracture cementation and crosscutting relationships corroborate the identification of three fracturing stages. U–Pb dating of fractured cement has widely detected Middle Ordovician and Early Permian age intervals. Fluid inclusion homogenization temperatures from the fractured cements, ranging across < 50 °C, 70–130 °C, and 150–180 °C, correspond to three episodes of rapid subsidence during the Ordovician, Permian, and Neogene, respectively. These results suggest three phases of fault/fracture reactivation in the Middle Ordovician (prior to 470 Ma), Early Permian (prior to 295 Ma), and Cenozoic. The fault/fracture reactivation in the Ordovician is closely related to the regional tectonic transition from extension to compression, while fault and fracture reactivation in the Early Permian may be related to hydrothermal activity associated with large-scale igneous province and oil emplacement. Fault/fracture activity in the Cenozoic may be related to a reduction in subsidence, gradual reduction of geothermal gradients, and massive oil emplacement. This research underscores the significance of integrating geochemical and subsurface datasets for accurately determining the timing of faulting and fracturing in sedimentary basins.