Evaluating estuary water quality responses to reductions (or increases) in nutrient loading attributed to on the ground management actions can be challenging due to the strong influence of environmental drivers on nutrient loads and non-linear relationships. This study applied generalized additive models to calculate watershed nutrient loads and assess responses in estuary water quality to seasonally-adjusted freshwater inflow and flow-adjusted nutrient loads in Lavaca Bay, Texas. Lavaca Bay is a secondary embayment on the Texas coast displaying early potential for eutrophication and water quality degradation. Use of flow-adjusted nutrient loads allowed the study to evaluate the response in water quality to changes in nutrient loads driven by anthropogenic sources. Cross-validation indicated that, despite data constraints, semiparametric models performed well at nutrient load prediction. Based on these models, delivered annual nutrient loads varied substantially from year to year. In contrast, minimal changes in flow-normalized loads indicate that nutrient loadings were driven by natural variation in precipitation and runoff as opposed to changes in management of nonpoint sources. Models indicated no evidence of long-term changes in dissolved oxygen or chlorophyll-a within Lavaca Bay. However, site specific long-term increases in both organic and inorganic nitrogen are concerning for their potential to fuel eutrophication. Further analysis found freshwater inflow had strong influences on nutrient and chlorophyll-a concentrations but there was no evidence that changes in watershed nutrient loading explained additional variation in dissolved oxygen and limited evidence that watershed nutrient loadings explained chlorophyll-a concentrations. In addition to providing a baseline assessment of watershed nutrient loading and water quality responses in the Lavaca Bay watershed, this study provides methodological support for the use of semiparametric models in load regression models and estuary assessments.