Human interventions during the last 70 years have altered the characteristics of the Gialova Lagoon, a coastal wetland that is part of a wider Natura 2000 site. In this study, we explore how human interventions and climate altered the wetland’s hydrological conditions and habitats, leading to changing wetland functions over time. Our interpretations are based on a mixed methodological approach combining conceptual hydrologic models, analysis of aerial photographs, local knowledge, field observations, and GIS (Geographic Information System) analyses. The results show that the combined effects of human interventions and climate have led to increased salinity in the wetland over time. As a result, the fresh and brackish water marshes have gradually been turned into open water or replaced by halophytic vegetation with profound ecological implications. Furthermore, current human activities inside the Natura 2000 area and in the surrounding areas could further impact on the water quantity and quality in the wetland, and on its sensitive ecosystems. We suggest that a more holistic understanding of the broader socio-ecological system is needed to understand the dynamics of the wetland and to achieve sustainable long-term management and conservation strategies.