Although many consequences of climate change on marine and terrestrial ecosystems are well documented, the characterisation of estuarine ecosystems specific responses and the drivers of the changes are less understood. In this study, we considered the biggest Southwestern European estuary, the Gironde, as a model of a macrotidal estuary to assess the effects of both large- (i.e., North Atlantic basin-scale) and regional-scale climate changes. Using a unique set of data on climatic, physical, chemical and biological parameters for the period 1978–2009, we examined relations between changes in both the physical and chemical environments and pelagic communities (plankton and fish) via an end-to-end approach. Our results show that the estuary experienced two abrupt shifts (!1987 and !2000) over the last three decades, which altered the whole system. The timing of these abrupt shifts are in accordance with abrupt shifts reported in both marine (e.g., in the North Sea, the Mediterranean Sea and along the Atlantic) and terrestrial (e.g., in European lakes) realms. Although this work does not allow a full understanding of the dynamical processes through which climate effects propagate along the different compartments of the ecosystem, it provides evidence that the dynamics of the largest estuary of Southwest Europe is strongly modulated by climate change at both regional and global scales.