The Ordovician–Silurian organic-rich shales in the Wufeng and Longmaxi Formations are widespread in southern China and are the most important shale gas producers in China. The shales display varying total organic carbon content ranging from 0.2% to 6% and are composed of black siliceous mudstone, shelly limestone, siliceous clay-rich mudstone, gray silty–shaly interlaminated mudstone, gray argillaceous mudstone, and calcareous or dolomitic mudstone. Detailed stratigraphic correlation of these formations was achieved, and a high-resolution sequence stratigraphy was constructed based on the integration of well-log data, mineralogical, geochemical, and petrophysical analyses. The Wufeng Formation and the Guanyinqiao Bed were interpreted to be a condensed section with four cycles of sea-level fluctuation. The Longmaxi Formation consists of three members. The Long-1 Member was interpreted to be a third-order depositional sequence that can be subdivided into a transgressive systems tract, an early highstand systems tract, and a late highstand systems tract. Within the constructed isochronal stratigraphic framework, the characteristics and genetic mechanism of different shale lithofacies were studied. The deposition of black siliceous mudstone of high total organic carbon in the Wufeng Formation and the Long-1 transgressive systems tract was likely influenced by volcanic activity. The Guanyinqiao shelly limestone or calcareous mudstone was associated with the Ordovician–Silurian transition when glaciation and mass extinction took place. The gray silty–shaly interlaminated mudstone of moderate total organic carbon in the Long-1 early highstand systems tract was the product of bottom flow intrusion. The deposition of gray argillaceous mudstone and calcareous or dolomitic mudstone with low total organic carbon in the Long-1 late highstand systems tract resulted from enhanced terrigenous input from peripheral uplifts. The distribution pattern of different lithofacies varies greatly in the Upper Yangtze area, and this difference is a result of dissimilar sediment provenances and variable hydraulic restriction levels that were controlled by basin geometry. A better understanding of the distribution pattern and depositional history of the Wufeng and Longmaxi Formations might provide guidance for future profitable shale gas exploration.