Most transboundary rivers and their wetlands are subject to considerable anthropogenic pressures associated with multiple and often conflicting uses. In the Eastern Mediterranean such systems are also particularly vulnerable to climate change, posing additional challenges for integrated water resources management. Comprehensive measurements of the optical signature of colored dissolved organic matter (CDOM) were combined with measurements of river discharges and water physicochemical and biogeochemical properties, to assess carbon dynamics, water quality, and anthropogenic influences in a major transboundary system of the Eastern Mediterranean, the Evros (or, Марица or, Meriç) river and its Ramsar protected coastal wetland. Measurements were performed over three years, in seasons characterized by different hydrologic conditions and along transects extending more than 70 km from the freshwater end-member to two kilometers offshore in the Aegean Sea. Changes in precipitation, anthropogenic dissolved organic matter (DOM) inputs from the polluted Ergene tributary, and the irregular operation of a dam were key factors driving water quality, salinity regimes, and biogeochemical properties in the Evros delta and coastal waters. Marsh outwelling affected coastal carbon quality, but the influence of wetlands was often masked by anthropogenic DOM contributions. A distinctive five-peak CDOM fluorescence signature was characteristic of upstream anthropogenic inputs and clearly tracked the influence of freshwater discharges on water quality. Monitoring of this CDOM fluorescence footprint could have direct applications to programs focusing on water quality and environmental assessment in this and other transboundary rivers where management of water resources remains largely ineffective.