Climate-driven changes in freshwater inputs have been shown to affect the structure and function of coastal ecosystems. We evaluated changes in the influence of river runoff on coastal systems of Northwestern Patagonia (NWP) over recent decades (1993–2021) by combined analysis of long-term streamflow time series, hydrological simulation, satellite-derived and reanalysis data on sea surface conditions (temperature, turbidity, and salinity). Significant decreases in minimum streamflow across a zone spanning six major river basins were evident at weekly, monthly, and seasonal scales. These changes have been most pronounced in mixed-regime northern basins (e.g., Puelo River) but appear to be progressing southward to rivers characterised by a nival regime. In the adjacent two-layer inner sea, reduced freshwater input corresponds with a shallower halocline and increased surface temperatures across northern Patagonia. Our results underscore the rapidly evolving influence of rivers on adjacent estuarine and coastal waters in NWP. We highlight the need for cross-ecosystem observation, forecasting, mitigation and adaptation strategies in a changing climate, together with corresponding adaptive basin management of systems that supply runoff to the coastal marine waters.