Inter-basin Water Transfers (IBWT) are recognized as one of the major pathways of freshwater invasion. They provide a direct link between previously isolated catchments and may modify the habitat conditions of the receiving waters such that they become more favourable for the establishment of invasive species. Combined, IBWT and invasive species will intensify the stress upon native species and ecosystems. Using the Severn and Thames Rivers -two of the largest river systems in Great Britain-as a case study, here we assess the potential influence of IBWT on the expansion of invasive species and thus their impact on biodiversity conservation. The Thames Valley is subject to extensive water abstraction, and an increasing population means that supplemented flow from the River Severn is being considered. Multi-scale Suitability Models, based on climate and water chemistry respectively, provided novel evidence that there is serious risk for further spread of invasive species in the focus area, particularly of the quagga mussel, a recent invader of the Thames River. Native freshwater mussels are particularly vulnerable to changing environmental conditions, and may suffer the decrease in alkalinity and increase in sedimentation associated with an IBWT from the lower Severn to the upper Thames. Regional models suggest considerable overlap between the areas suitable for three vulnerable native freshwater mussels and the expansion of invasive species that negatively impact upon the native mussels. This study illustrates the use of novel spatially-explicit techniques to help managers make informed decisions about the risks associated with introducing aquatic invasive species under different engineering scenarios. Such information may be especially important under new legislation (e.g. EU Invasive Species Regulation No 1143/2014) which increases the responsibility of water managers to contain and not transfer invasive species into new locations.