Numerical models are often used to simulate estuarine physics and water quality under scenarios of future climate conditions. However, representing the wide range of uncertainty about future climate often requires an infeasible number of computationally expensive model simulations. Here, we develop and test a computationally inexpensive statistical model, or metamodel, as a surrogate for numerical model simulations. We show that a metamodel fit using only 12 numerical model simulations of Chesapeake Bay can accurately predict the early summer mean salinity, stratification, and circulation simulated by the numerical model given the input sea level, winter–spring streamflow, and tidal amplitude along the shelf. We then use this metamodel to simulate summer salinity and circulation under sampled probability distributions of projected future mean sea level, streamflow, and tidal amplitudes. The simulations from the metamodel show that future salinity, stratification, and circulation are all likely to be higher than present-day averages. We also use the metamodel to quantify how uncertainty about the model inputs transfers to uncertainty in the output and find that the model projections of salinity and stratification are highly sensitive to uncertainty about future tidal amplitudes along the shelf. This study shows that metamodels are a promising approach for robustly estimating the impacts of future climate change on estuaries.