Understanding and managing the susceptibility of lakes to anthropogenic eutrophication has been a primary goal of limnological research for decades. To achieve United Nations’ Sustainable Development Goals, scientists have attempted to understand why shallow lakes appear to be prone to eutrophication and resistant to restoration. A rich data base of 1151 lakes (each ≥ 0.5 km2 located within the Europe and the United States of America offers a rare opportunity to explore potential answers. Analysis of sites showed that lake depth integrated socio-ecological systems and reflected potential susceptibility to anthropogenic stressors, as well as lake productivity. In this study, lakes distributed in agricultural plain and densely populated lowland areas were generally shallow and subjected to intense human activities with high external nutrient inputs. In contrast, deep lakes frequently occurred in upland regions, dominated by natural landscapes with little anthropogenic nutrient input. Lake depth appeared to not only reflect external nutrient load to the lake, but also acted as an amplifier that increased shallow lake susceptibility to anthropogenic disturbance. Our findings suggest that shallow lakes are more susceptible to human forcing and their eutrophication may be not an occasional occurrence, and that societal expectations, policy goals, and management plans should reflect this observation.