In this study, we analyzed the impacts of different environmental conditions on aquatic worm communities along the Danube River, based on two longitudinal surveys, the Joint Danube Surveys 2 and 3 (JDS; 2007 and 2013). We identified the most important environmental factors (among analyzed groups) that shape worm communities: hydromorphlogical alterations, flow velocity and substrate (HYMO group), dissolved oxygen, nitrates and nitrites (physico-chemical parameters), zinc and nickel (metals), monobutyltin cation, benzo(b) fluoranthene and benzo(k)fluoranthene, polychlorinated biphenyls PCB 77 and PCB 118 (selected chemical determinants—organotin compounds, Polycyclic aromatic hydrocarbons—PAHs and PCBs). A homogenization of species composition of Oligochaeta assemblages along the Danube was confirmed. As one of main factors related to biotic homogenization, hydromorphological alterations represented by similar changes in flow velocity and substrates along Danube’s course could be singled out. Our results indicate that Oligochaeta could be used for the identification of the level of hydromorphological degradation in large rivers (homogenization), rather than for stressors classified as nutrient and organic pollutants. Our results provide additional evidence in risk assessment of the environment, contributing in water management and monitoring of the ecological status as proposed by the Water Framework Directive.