Salinity dynamics in the Delaware Bay estuary are a critical water quality concern as elevated salinity can damage infrastructure and threaten drinking water supplies. Current state-of-the-art modeling approaches use hydrodynamic models, which can produce accurate results but are limited by significant computational costs. We developed a machine learning (ML) model to predict the 250 mg L⁻¹ Cl⁻ isochlor, also known as the “salt front,” using daily river discharge, meteorological drivers, and tidal water level data. We use the ML model to predict the location of the salt front, measured in river miles (RM) along the Delaware River, during the period 2001–2020, and we compare predictions of the ML model to the hydrodynamic Coupled Ocean–Atmosphere-Wave-Sediment Transport (COAWST) model. The ML model predicts the location of the salt front with greater accuracy (root mean squared error [RMSE] = 2.52 RM) than the COAWST model does (RMSE = 5.36); however, the ML model struggles to predict extreme events. Furthermore, we use functional performance and expected gradients, tools from information theory and explainable artificial intelligence, to show that the ML model learns physically realistic relationships between the salt front location and drivers (particularly discharge and tidal water level). These results demonstrate how an ML modeling approach can provide predictive and functional accuracy at a significantly reduced computational cost compared to process-based models. In addition, these results provide support for using ML models in operational forecasting, scenario testing, management decisions, hindcasting, and resulting opportunities to understand past behavior and develop hypotheses.