Submarine groundwater discharge (SGD) has received increasing attention by studies on coastal areas; however, its effects on biogeochemical zonation have not been investigated to date. The Huanghe River Estuary (HRE) is a world class river estuary with high turbidity, and heavy human regulation. This study investigated how SGD is related to the benthic biogeochemistry of the HRE. Based on the distribution of several parameters (e.g., salinity, temperature, dissolved oxygen (DO) levels, pH, radium isotopes, and nutrients), the HRE was subdivided into six different zones, and the SGD fluxes within each zone were quantified and compared. The highest SGD flux was found in the northwest nearshore zone, where it was more than one order of magnitude higher than in the offshore zone. High SGD resulted in low DO and pH, but high nutrient levels in the benthic boundary layer. The southeast nearshore zone was also characterized by high SGD flux, but benthic waters were more oxic because of the dominating inputs by the Huanghe River. These data suggest that such a zonation would help to understand benthic biogeochemical processes. High SGD may not only contribute to the estuarine nutrient budget, but may also contribute to the formation of hypoxia and acidification.