Several factors can affect virus behavior and persistence in water sources. Historically linear models have been used to describe persistence over time; however, these models do not consider all of the factors that can affect inactivation kinetics or the observed patterns of decay. Meanwhile, applying the appropriate persistence model is critical for ensuring that decision makers are minimizing human health risk in the event of contamination and exposure to contaminated groundwater. Therefore, to address uncertainty in predictions of decay or virus concentrations over time, this study fit seventeen different linear and nonlinear mathematical models to persistence data from a previously conducted sampling study on drinking water wells throughout the United States. The models were fit using Maximum Likelihood Estimation and the best fitting models were determined by the Bayesian Information Criterion. The purpose of the study was to identify the best model for estimating decay of viruses in groundwater and to determine if model uncertainty contributes to erroneous predictions of viral contamination when only conventional models are considered. For the datasets analyzed in this study, the Juneja and Marks models and the exponential damped model were more representative of the persistence of viruses in groundwater than the traditionally used linear models. The results from this study were then evaluated with classification trees in order to identify more relevant modeling methodology for future research. The classification trees aid in narrowing the scope of appropriate persistence models based on characteristics of the experimental conditions and water sampled.