Due to the geographical circumstances, the Yangtze River Estuary (YRE) and the adjacent East China Sea are extensively influenced by both anthropogenic activities and environmental factors. To reveal the responses of microbes in surface sediment to environmental factors and their contributions to the biogeochemical cycle in this area, surface sediment and overlying water samples were collected at 21 stations from the estuary to the coastal region. Water and sediment parameters were determined, and 16S rRNA genes of microbes in sediment samples were sequenced using high throughput sequencing technology. The results indicated that ocean currents, sediment density (SD), nutrients, sulfate (SO₄^2-), and salinity were the key factors shaping the microbial communities. Coastal microbes were affected mainly by SD, whereas anthropogenic discharge might have been responsible for a decrease in indigenous microbial diversity in the ocean. Due to the anthropogenic discharge, the most representative bacteria in the nearshore were aerobic and chemoheterotrophic bacteria, including ammonia-oxidizing bacteria, nitrite-oxidizing bacteria, denitrifying bacteria, and polyphosphate accumulating organisms. In the offshore, anaerobic bacteria, thermophilic bacteria, halophilic bacteria, sulfate-reducing bacteria, and sulfide oxidizing bacteria were the dominant bacteria, and these were characterized by strong solidarity and cooperative properties within the malnourished environment. In summary, these results provide a new perspective for revealing the biogeochemical significance of the bacterial lineages in the YRE, as well as constructive guidance for the management of the marginal sea ecosystems in distinct regions.