Coastal zones are active reactors of continental material including that transported by rivers via a series of microbiota-mediated reactions. Nevertheless, current knowledge of the ecology and functioning of the microbiota in coastal areas affected by large riverine inputs remains insufficient on a global scale. Here, an investigation on sediment microbial composition, including taxonomy and metabolic network, as well as their relationship with major benthic reaction substrates, namely carbon, nitrogen, sulphur and phosphorus, was conducted in the continental shelf affected by the spread of the Changjiang River plume. Surface sediment samples (48 samples) were collected during March 2018, obtaining a mean Operational Taxonomic Units (OTUs) number of 3341. Proteobacteria, Acidobacteria and Actinobacteria were abundant phyla in the studied sediments. Bray-Curtis distance analysis classified the 48 samples into 4 clusters (MG1 to MG4) at the phylum-level. MG1 and MG2 are found near the river mouth, receiving substantial land-derived particles from the Changjiang River runoff. Particle-attached microbes may be settled in these regions and influenced the observed sediment microbial diversity and biomass, e.g., increased Crenarchaeota relative abundance. The relative enrichment of these two groups in heterotrophic microbes further suggests a reliance of benthic microbiota on substrates with terrestrial origin, particularly specialized on processing sulphur-rich substrates. Regions MG3 and MG4 are located in the outer margin of the area affected by the Changjiang River plume, mainly fed by settling pelagic particles from phytoplankton. Compared to MG1 and MG2, a significant increase in the abundance of Thaumarcheota (phylum-level) and Nitrosopumilus (genus-level) was found in MG3, suggesting nitrogen-related transformations as the key reactions to sustain microbial metabolism in this region. Coupled with the identified variations in the taxonomic composition, significant differences in the keystone taxa between MG1/MG2 and MG3/MG4 were identified via OTU co-occurrence analyses. A higher abundance of Actinobacteria, Thaumarchaeota and Acidobacteria in MG3 and MG4 reinforced the identified spatial variability in benthic metabolism and highlighted the significance of substrate inputs on the sediment microbial structure and biogeography.