Salinity management is a subject of particular interest in estuarine environments because of the underlying biological significance of salinity and its variations in time and space. The foremost step in such management practices is understanding the spatial and temporal variations of salinity and the principal drivers of these variations. This has traditionally been achieved with the assistance of empirical or process-based models, but these can be computationally expensive for complex environmental systems. Model emulation based on data-driven methods offers a viable alternative to traditional modeling in terms of computational efficiency and improving accuracy by recognizing patterns and processes that are overlooked or underrepresented (or overrepresented) by traditional models. This paper presents a case study of emulating a process-based boundary salinity generator via deep learning for the Sacramento–San Joaquin Delta (Delta), an estuarine environment with significant economic, ecological, and social value on the Pacific coast of northern California, United States. Specifically, the study proposes a range of neural network models: (a) multilayer perceptron, (b) long short-term memory network, and (c) convolutional neural network-based models in estimating the downstream boundary salinity of the Delta on a daily time-step. These neural network models are trained and validated using half of the dataset from water year 1991 to 2002. They are then evaluated for performance in the remaining record period from water year 2003 to 2014 against the process-based boundary salinity generation model across different ranges of salinity in different types of water years. The results indicate that deep learning neural networks provide competitive or superior results compared with the process-based model, particularly when the output of the latter are incorporated as an input to the former. The improvements are generally more noticeable during extreme (i.e., wet, dry, and critical) years rather than in near-normal (i.e., above-normal and below-normal) years and during low and medium ranges of salinity rather than high range salinity. Overall, this study indicates that deep learning approaches have the potential to supplement the current practices in estimating salinity at the downstream boundary and other locations across the Delta, and thus guide real-time operations and long-term planning activities in the Delta.