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A preliminary sequence stratigraphic geochemical investigation was carried out to assess the areal distribution and hydrocarbon generation potential of marine mudstones of the Upper Cretaceous Yogou Formation in the Termit Basin, Niger. A total of three third‐order sequences (YSQ1, YSQ2, and YSQ3, from bottom to top) and nine systems tracts were identified in the Yogou Formation. Mudstones of each sequences are widely distributed throughout the study area with their maximum cumulative thickness of ~600–900 m in the Dinga and Moul depressions. The ΔlogR method was applied to establish a prediction model for predicting the total organic carbon (TOC) content of the Yogou Formation mudstones. The results of this source rock evaluation indicate that thick offshore mudstones with fair to good hydrocarbon generation potential and dominated Type II to Type III kerogen widely occur in YSQ1, YSQ2, and in the LST (lowstand systems tract) and TST (transgressive systems tract) of YSQ3, while the thin lower shoreface mudstone intervals in the HST (highstand systems tract) of YSQ3 are characterized by good to excellent hydrocarbon generation potential, dominated by Type II kerogen. The present‐day thermal maturation level of source beds from the YSQ3, YSQ2, and YSQ1 has overpassed the main zone of oil generation in the depocenter of Dinga Depression, whereas the YSQ3 and part of YSQ2 source beds were still within the oil window in the depocenter of Moul Depression. The organic matter richness and hydrocarbon generation potential of source beds varies within the Yogou Formation because of changes in organic matter source during evolution of Western Africa rift basins and global sea‐level fluctuations. This study provides a practical sequence stratigraphic geochemical framework which will give a better understanding for the geochemical characteristics of source rock and support improved assessment of petroleum resources.