During the Middle Ordovician, the Great Ordovician Biodiversification Event (GOBE) saw an accelerated diversification pulse in the marine metazoan richness, which has been linked to the oceanic and climatic changes. Here we have examined a deep-water slope succession, Xijinhe section, in Lower Yangtze region by integrating sedimentological and geochemical methods. This study highlights that the climatic and oceanic destabilization might have substantially impacted the marine biodiversity during the Middle Ordovician in South China. Three phases are identified based on lithological and geochemical variations. During Phase I across the Early–Middle Ordovician transition (Floian–Dapingian), the TOC and abundances of redox sensitive elements (RSE) are relatively depleted, suggesting a suboxic-oxic environment in the slope area of Yangtze Sea. The continental chemical weathering intensity transits from stable to unstable in Phase I indicated by CIA (chemical index of alteration) that gradually fluctuate to lower values, potentially caused by the secular cooling. The slowly ameliorating climate and redox conditions advanced the biodiversification across the Early–Middle Ordovician transition. During the Phase II in the Darriwilian, the continental chemical weathering intensity continues to decrease and the concentrations of RSE start to rise. The values of Mn(%)*Co(ppm) become consistently lower than 0.4, and the bio-limited elements such as P, Ba, and Ni are substantially enriched correspondingly. This phenomenon implicates that a secular cooling climate would have resulted in oceanic destabilization by improving upwelling of deeper anoxic/euxinic and eutrophic water into epicontinental sea, potentially causing a deceleration in the biodiversification during the Darriwilian in South China. The Phase III across the Middle–Late Ordovician transition, witnesses the continuous decrease of CIA values and highest abundances of TOC and RSE though some minor fluctuations, indicating a possibly even more drastic oceanic destabilization relative to Phase II. Deeper anoxic/euxinic water continuously intruded and shoaled into the shelf area during the Phase III due to the enhanced upwelling. Consequently, the habitat of marine organisms in shallow water was contracted, and becoming harsher. Additionally, bio-limited elements such as P were released from anoxic sediments and recycle into the seawater during the Middle Ordovician, boosting primary productivity level and may further deplete oxygen in seawater. This unstable oceanic state during the Middle Ordovician, particularly Darriwilian, represented by high nutrients content in epi-continental sea and expanding anoxic/euxinic water, could be attributable for the deceleration of biodiversification in South China and potentially the spatially variable paces of biodiversification in different paleo-continents during the main phase of the GOBE.