The use of coastal-marine resources is currently based on an unsustainable development model that leads to deterioration of the environment and consequent reductions in economic activities and the well-being of coastal societies. According to the conceptual framework provided by the sustainable blue economy model, this paper evaluates the effects of anthropogenic activities on the ecosystem services (ESs) of the coastal areas of the island and the sea of Chiloe, an archipelago located in Chilean Patagonia. It also analyzes how the degradation of the environment ultimately affects the economy itself and human well-being. The methodology employed is based on the construction of three matrices that connect 12 economic activities identified in the study area, with three ESs groupings (provisioning, regulating, and cultural) and four components of human well-being (security, material assets, health, and social relations). The impacts are assessed using four categories: high impact (3), moderate impact (2), low impact (1), and positive impact (0). The results reflect the domination of economic sectors that negatively affect the environment, among which salmon farming, the main activity in Chiloe, stands out. In contrast, small-scale fishing has been the highest evaluated sector, largely because of the new management instruments that have been developed in Chile. The establishment of a sustainable blue economy in Chiloe requires the application of sustainability standards –such as those proposed for small-scale fisheries– in the sectors that generate the most socio-ecological impacts.