The effects of Cd-rich venting fluids on the Cd contents and isotopic compositions of continental margin sediments remain poorly understood. Characterization of the Cd isotopic composition of sediment overprinted by venting fluids is critical, as this may provide insights into how mixing between the venting fluids and bottom waters affects the Cd isotopic composition. Our study determined the Cd isotopic compositions of Lower Cambrian metalliferous sediment deposited on the passive continental margin of the southeastern Yangtze Block, South China. The Cd is predominantly hosted in sphalerite of sulfide-bearing barite sediments, V deposits, and Ni-Mo−platinum group element (PGE) sulfide layers. The Cd isotopic compositions of samples from these three units indicate that the distribution of Cd at this type of continental margin was controlled by submarine hydrothermal activity. Following the venting of hydrothermal fluids onto the seafloor, Cd2+ reacted with a limited amount of H2S generated mainly by thermochemical sulfate reduction near the vents. This resulted in isotopically lighter Cd in the sulfide-bearing barite sediments and V deposits, which have δ114/110Cd values of 0.00‰ ± 0.13‰ and 0.00‰ ± 0.14‰, respectively. The residual dissolved Cd in the fluids migrated with the upwelling seawater and ultimately precipitated almost entirely as sphalerite in the sulfidic wedge, which resulted in Ni-Mo−PGE sulfide layers with a narrow range of high δ114/110Cd values (0.35‰ ± 0.03‰). The presence of Cd-rich venting fluids can alter the Cd contents and isotopic compositions of passive margin sediments, particularly those located within long-term stratified seawater and fault depressions. Previous studies may have underestimated the migration distance and affected areas of hydrothermal activity involving Cd-rich fluids.