Introduction: Climate change is reducing freshwater availability worldwide, making it essential to understand how freshwater inflow influences estuarine ecosystem functioning and marine fisheries productivity. In the Gulf of Cádiz (SW Spain), one of the most important fishing areas in Spain, the Guadalquivir Estuary serves as a key nursery habitat for commercially important fish and crustacean species. Objective: The aim of this study is to evaluate the effects of droughts and floods on estuarine functioning and coastal fisheries. Methodology: We analyzed 25 years of monthly data (1997–2022) from the Guadalquivir Long-Term Ecological Research Program (GUADALQUIVIR-LTER), using time-series analyses and dynamic structural equation modelling. Environmental variables, zooplankton and mysid biomass, and juvenile biomass of anchovy, sardine, and meagre were examined to assess trophic relationships and recruitment dynamics. Results: Our findings show that positive North Atlantic Oscillation (NAO) phases, associated with drought conditions in southern Europe, reduced freshwater inflow from the Alcalá del Río Dam into the estuary. Freshwater input increased organic matter and turbidity, which positively affected the mysid Rhopalophthalmus tartessicus, an important prey species for anchovy recruits. The mysid Mesopodopsis slabberi showed the strongest positive effect on anchovy recruitment (0.39). Although turbidity initially had a negative effect on M. slabberi, a significant positive effect appeared after monthly lag = 4. Conclusions: These findings demonstrate that spring freshwater inflow is essential for maintaining estuarine productivity, enhancing mysid abundance, and supporting anchovy recruitment, ultimately benefiting adult fish stocks after juveniles migrate from the estuary to coastal waters.