Variations in estuarine carbonate chemistry can have critical impacts on marine calcifying organisms, yet the drivers of this variability are difficult to quantify from observations alone, due to the strong spatiotemporal variability of these systems. Terrestrial runoff and wetland processes vary year to year based on local precipitation, and estuarine processes are often strongly modulated by tides. In this study, a 3D-coupled hydrodynamic-biogeochemical model is used to quantify the controls on the carbonate system of a coastal plain estuary, specifically the York River estuary. Experiments were conducted both with and without tidal wetlands. Results show that on average, wetlands account for 20–30% of total alkalinity (TA) and dissolved inorganic carbon (DIC) fluxes into the estuary, and double-estuarine CO2 outgassing. Strong quasi-monthly variability is driven by the tides and causes fluctuations between net heterotrophy and net autotrophy. On longer time scales, model results show that in wetter years, lower light availability decreases primary production relative to biological respiration (i.e., greater net heterotrophy) resulting in substantial increases in CO2 outgassing. Additionally, in wetter years, advective exports of DIC and TA to the Chesapeake Bay increase by a factor of three to four, resulting in lower concentrations of DIC and TA within the estuary. Quantifying the impacts of these complex drivers is not only essential for a better understanding of coastal carbon and alkalinity cycling, but also leads to an improved assessment of the health and functioning of coastal ecosystems both in the present day and under future climate change.