This study uses a simulation method to explore how estuarine pH is affected by mixing between river water, anthropogenic CO2 enriched seawater, and by respiration. Three rivers with different levels of weathering products (Amazon, Mississippi, and St. Johns) are selected for this simulation. The results indicate that estuaries that receive low to moderate levels of weathering products (Amazon and St. Johns) exhibit a maximum pH decrease in the midsalinity region as a result of anthropogenic CO2 intrusion. This maximum pH decrease coincides with a previously unrecognized mid-salinity minimum buffer zone (MBZ). In addition, water column oxygen consumption can further depress pH for all simulated estuaries. We suggest that recognition of the estuarine MBZs may be important for studying estuarine calcifying organisms and pH-sensitive biogeochemical processes.