River biota are affected by global reach-scale pressures, but most approaches for predicting biota of rivers focus on river reach or segment scale processes and habitats. Moreover, these approaches do not consider long-term morphological changes that affect habitat conditions. In this study, a modelling framework was further developed and tested to assess the effect of pressures at different spatial scales on reach-scale habitat conditions and biota. Ecohydrological and 1D hydrodynamic models were used to predict discharge and water quality at the catchment scale and the resulting water level at the downstream end of a study reach. Long-term reach morphology was modelled using empirical regime equations, meander migration and 2D morphodynamic models. The respective flow and substrate conditions in the study reach were predicted using a 2D hydrodynamic model, and the suitability of these habitats was assessed with novel habitat models. In addition, dispersal models for fish and macroinvertebrates were developed to assess the re-colonization potential and to finally compare habitat suitability and the availability/ability of species to colonize these habitats. Applicability was tested and model performance was assessed by comparing observed and predicted conditions in the lowland Treene River in northern Germany. Technically, it was possible to link the different models, but future applications would benefit from the development of open source software for all modelling steps to enable fully automated model runs. Future research needs concern the physical modelling of long-term morphodynamics, feedback of biota (e.g., macrophytes) on abiotic habitat conditions, species interactions, and empirical data on the hydraulic habitat suitability and dispersal abilities of macroinvertebrates. The modelling framework is flexible and allows for including additional models and investigating different research and management questions, e.g., in climate impact research as well as river restoration and management.