Estuaries are very productive habitats that serve as spawning and nursery grounds for fisheries species. The Rio de la Plata (RdP) Estuary and its maritime front sustain valuable fisheries for Argentina and Uruguay. Micropogonias furnieri, the coastal fish species historically representing highest catches, has declined landings in recent decades. To enhance our understanding on how natural variability influences this resource and improves its management, we analysed the effect of environmental conditions on M. furnieri’s commercial landings in the long term using generalized linear and additive models (GLMs and GAMs). Explanatory variables, with up to a 10-year lag, included sea surface temperature, turbidity, salinity, wind, river runoff, and climatological indices: El Niño-Southern Oscillation (ENSO), the Southern Annular Mode (SAM) and the Southern Oscillation Index (SOI). Time-lagged analyses for single-covariate models reveal higher deviances explained (DE) at 2, 6, 7, and 8-year lags. Turbidity and salinity, followed by wind and temperature, are the most common variables affecting catches of M. furnieri for GLMs and GAMs. The absence of significant models with only climatological indices or river discharge indicates the impact of large-scale climate fluctuations and river runoff on the RdP Estuary conditions. The best-fitting GLM model includes SAM, turbidity, and wind (DE = 78.8%), whereas the GAM model includes turbidity and wind (DE = 86.4%). Sensitivity of M. furnieri’s catches to climatic signals (ENSO, SAM, SOI) is described for the first time. Our findings provide insights for authorities to implement management measures beyond fishing quotas encompassing environmental shifts in the long-term.