Due to decades of persistent anthropogenic pressures, lowland rivers represent one of the most severely impaired habitats in Europe. Despite improved water quality, novel stressors, particularly climate change, are emerging with most lowland rivers suffering from past hydromorphological degradation. We aim to elucidate how such degradation alters the biological response in multiple-stressor environments, as this has rarely been considered in studies documenting long-term development of anthropogenically impacted rivers. Here, benthic macroinvertebrates, water quality and hydroclimatic variables were monitored over a period of two decades in nine of the largest Czech rivers. Detailed data on hydromorphological degradation allowed us to track distinct patterns in rivers with high and low levels of degradation. Temporal changes in environmental variables showed similar patterns in both site groups, characterised by reduced organic and nutrient pollution but increased hydroclimatic and salinity stress. 150 % increase in total abundance, especially in abundance and richness of sediment-dwelling and non-native taxa was found in both site groups. While the increase in abundance was due to improved water quality and rising water temperature, the longer duration of minimal flows had a negative effect on species richness, hampering species gain particularly at highly degraded sites. Our results provide novel evidence that degree of hydromorphological degradation modifies long-term macroinvertebrate responses to anthropogenic pressures. Less degraded sites displayed several favourable changes, such as 27 % increase in total and 23 % increase in potamal indicator richness, and stabilisation of the assemblages with few functional changes. In contrast, highly degraded sites experienced 9 % reduction in evenness, 235 % increase in proportion of non-native taxa and functional reorganisation, changes congruent with continuous deterioration. While overall water quality at studied sites has improved, consequences of climate change and high degree of hydromorphological degradation limit biotic recovery in multiple-stressor lowland rivers.