The invasion of alien species can have serious economic and ecological impacts. Ecologically, invasions often lead to an increased rate of native species replacement and decreased biodiversity. A critical step in the dominance of alien species is their successful co-occurrence with native species. In this study, we assessed the occurrence of alien molluscs and their co-occurrence with native molluscs and identified the determining physical-chemical variables. We expected that a combination of some key variables of water quality could provide suitable conditions promoting alien molluscs to occur and to co-occur with native molluscs. The analyses were based on 20-year data, collected from river systems across Flanders (Belgium). Classification Trees (CTs) were used to perform the analyses and to develop the predictive models. Based on CT models, the co-occurrence of alien and native molluscs could be reliably predicted based on physical-chemical variables. However, there was insufficient data to determine the environmental conditions in which alien taxa dominate. From the past to the present, spatial co-occurrence significantly increased. Sinuosity, ammonium and nitrate concentrations, chemical oxygen demand, pH and conductivity were the key determining variables. Our findings suggest that the co-occurrence of alien and native molluscs mainly occurs in straight rivers with good chemical water quality. These results provide insights into the ecology and behaviour of alien species which could support management practices and priority setting for conservation planning in surface waters of Flanders and Europe.