In this chapter, we use mathematical modeling to explore the dynamics of key fish populations in the Chesapeake Bay. These fisheries are vital renewable resources that support the economic well-being of local communities while contributing to the biodiversity and ecological stability of the largest estuary in the United States. We begin with single-species population modeling, using logistic growth to fit real observational data. We then extend our analysis to two-species systems by fitting the generalized Lotka–Volterra model to laboratory predator–prey data as well as to field data on Atlantic menhaden and striped bass. Parameter sensitivity analysis, using both local and global methods, is incorporated to evaluate model robustness and highlight how small parameter variations influence population outcomes. Building on this, we derive a three-species model to study interactions among Atlantic menhaden as prey and two predators: the striped bass and the invasive blue catfish. Using a combination of theoretical analysis and computational simulations, we investigate whether harvesting blue catfish could serve as an effective population control strategy. Analytical tools include polynomial root-finding, eigenvalue and eigenvector analysis, the Routh–Hurwitz criteria, and the Hartman–Grobman theorem. Numerical simulations in MATLAB are used throughout to visualize system dynamics and explore long-term population behavior.