During the Eocene-Miocene period, Eastern China underwent significant tectonic reorganization, but some details of this evolution remain unclear. Newly collected Eocene-Miocene cores from Well ZK-wh001 in the Guzhen Basin, situated on the southeastern margin of the North China Block, offer a valuable opportunity to study sedimentary evolution and provenance changes in the Guzhen Basin during the Eocene-Miocene and document tectonic events during the Palaeogene-Neogene in Eastern China. Integrated sedimentology, heavy mineral analysis, elemental geochemistry, and detrital zircon chronology data reveal that the early Eocene Tujinshan Formation represents a lacustrine regressive succession from semi-deep lacustrine to shallow lacustrine and shore lacustrine facies, whereas the lower-middle members of the early Miocene Xiacaowan Formation are characterized by alluvial-fan succession, while its upper member reflects a braided fluvial system. Detrital zircon age spectra and heavy mineral assemblages indicate that both the Tujinshan Formation and the lower- middle members of the Xiacaowan Formation are mainly sourced from the Bengbu Uplift, but the upper member of the Xiacaowan Formation contains Jurassic-Early Cretaceous and Triassic detrital zircons, suggesting contributions from the Hefei Basin. Two unconformities among the Tujinshan Formation, the lower-middle members of the Xiacaowan Formation, and the upper member of the Xiacaowan Formation, have been proposed based on these sedimentary and provenance changes and seismic profiles. We interpret that the lower unconformity between the Tujinshan and Xiacaowan formations reflects a response to the Pacific Plate subduction event, triggering regional uplift across Eastern China, while the upper unconformity within the Xiacaowan Formation likely represents a far-field effect of the Indian-Eurasia collision, inducing differential uplift between the Hefei Basin and Guzhen Basin and driving provenance changes in the Guzhen Basin.