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• Native crayfish predominantly inhabit partially to highly fragmented freshwaters. • Native crayfish populations face moderate to high levels of threat. • Large uninvaded river sections can potentially be occupied by signal crayfish. Indigenous crayfish species (ICS) have suffered a significant decline in recent decades due to various threats including anthropogenic habitat degradation with resulting fragmentation, and the introduction of non-indigenous crayfish species (NICS). However, only a few studies have assessed and quantified these threats on a broad landscape scale. We aim to highlight the impact of these interacting pressures within the Sava and Drava basins in Slovenia, Croatia, and Hungary. Our aims were to (1) asses the fragmentation caused by artificial and natural barriers; (2) calculate a threat index using fragmentation, spatial distances to established NICS populations, urban settlements and roads; (3) conduct current habitat suitability modeling (HSM) using various biotic and abiotic environmental parameters. The target species in this area are the ICS Astacus astacus , Austropotamobius torrentium and Pontastacus leptodactylus as well as the invasive NICS Pacifastacus leniusculus and Faxonius limosus. Our analyses revealed that the Croatian and Hungarian segments of the Drava and Sava basins exhibit relatively low fragmentation levels, whereas the Slovenian basins are highly fragmented mainly due to a dense hydropower network. All ICS populations within each sub-basin in the study area are moderately to highly threatened according to our threat index calculation. The HSM showed, that only 14.1% and 11.6% of freshwater habitats are suitable for A. torrentium and A. astacus , respectively. In contrast, NICS could occupy substantial portions (up to 22%) of the total riverscape. The results affirmed the highly alarming situation, as native crayfish were once widely distributed across less unfragmented freshwaters of the Danube basin. Our analyses and findings will be helpful to enhance the existing frameworks for safeguarding the remaining ICS populations, predicting the possible spread of NICS, and help to improve sustainable management practices for freshwater ecosystems. [ABSTRACT FROM AUTHOR]