The Mesozoic–Cenozoic tectonic movement largely controls the northwest region of the Junggar Basin (NWJB), which is a significant area for the exploration of petroleum and sandstone-type uranium deposits in China. This work collected six samples from this sedimentary basin and surrounding mountains to conduct apatite fission track (AFT) dating, and utilized the dating results for thermochronological modeling to reconstruct the uplift history of the NWJB and its response to hydrocarbon migration and uranium mineralization. The results indicate that a single continuous uplift event has occurred since the Early Cretaceous, showing spatiotemporal variation in the uplift and exhumation patterns throughout the NWJB. Uplift and exhumation initiated in the northwest and then proceeded to the southeast, suggesting that the fault system induced a post spread-thrust nappe into the basin during the Late Yanshanian. Modeling results indicate that the NWJB mountains have undergone three distinct stages of rapid cooling: Early Cretaceous (ca. 140–115 Ma), Late Cretaceous (ca. 80–60 Ma), and Miocene–present (since ca. 20 Ma). These three stages regionally correspond to the Lhasa-Eurasian collision during the Late Jurassic–Early Cretaceous (ca. 140–125 Ma), the Lhasa-Gandise collision during the Late Cretaceous (ca. 80–70 Ma), and a remote response to the India-Asian collision since ca. 55 Ma, respectively. These tectonic events also resulted in several regional unconformities between the J3/K1, K2/E, and E/N, and three large-scale hydrocarbon injection events in the Piedmont Thrust Belt (PTB). Particularly, the hydrocarbon charge event during the Early Cretaceous resulted in the initial inundation and protection of paleo-uranium ore bodies that were formed during the Middle–Late Jurassic. The uplift and denudation of the PTB was extremely slow from 40 Ma onward due to a slight influence from the Himalayan orogeny. However, the uplift of the PTB was faster after the Miocene, which led to re-uplift and exposure at the surface during the Quaternary, resulting in its oxidation and the formation of small uranium ore bodies.