Nitrogen is an essential nutrient to form amino acids for fauna and flora. Its compound ammonia, however, is also one of the most important contaminants in an aquatic environment for its highly toxic nature and ubiquity in the surface water. Monitoring and controlling the total ammonia nitrogen are vital for human health and sustainable economic development. This paper attempts to develop an optimal model to monitor and predict the development of total ammonia nitrogen in a water body. A case study was carried out in the Houston Ship Channel and Galveston Bay in Texas, which aquatic environment is a nursery and spawning ground for diverse types of marine life. Meanwhile, the Bay also assimilates ammonia pollutants from Texas’s municipal and industrial wastewater. The toxic threat of total ammonia nitrogen in the bay was assessed, based on observed samples and forecasted values. Forty years of samples were collected from the Texas Commission on Environmental Quality. Correlations analysis was conducted between all physical, biological and chemical parameters and the total ammonia nitrogen. The trends of total ammonia nitrogen were modeled through a multivariate regression and an auto-regression, followed by an estimation of hazard quotient. The outcome shows that the total ammonia nitrogen in this study area is spatially correlated. For upstream flow, most measured parameters were highly correlated with the total ammonia nitrogen, whereas for downstream flow, weak correlations were noticed. Modeling results indicate that the auto-regression models can better fit the observed data than the multivariate regression models. Meanwhile, the predicted total ammonia nitrogen and the hazard quotient will remain at a lower level, meeting the ambient water criteria continuous concentration.