The Mobile–Tensaw Delta–Mobile Bay system encompasses a mosaic of habitats that sustain rich ecological diversity and valuable fishery resources. Quantifying the hydrographic variability and habitat trends of this system is essential for assessing fisheries dynamics and informing effective resource management. However, such efforts are complicated by the highly transient nature of river–estuary interactions, the shallow and spatially heterogeneous morphology, and gradual but persistent climatic influences. To address this knowledge gap, we conducted a 56-year high-resolution hindcast (1970–2025) using a cross-scale coastal ocean model. The model outputs were analyzed to elucidate interannual and decadal patterns in temperature, salinity, and habitat extent, providing insights into long-term environmental trends. Furthermore, the relationships between these hydrographic trends and major forcing factors, including river discharge variability, navigation channel deepening, and El Niño–La Niña oscillations, were examined to identify the primary drivers of system change. The resulting datasets establish a robust quantitative foundation for fishery stock assessments and provide scientifically grounded insights to guide ecosystem-based management of living resources in the Mobile Bay region.