Globally-threatened freshwater mussels belonging to the order Unionida (Bivalvia) may be adversely affected by dense beds of submerged macrophytes that modify habitat at the sediment-water interface. Such effects can be particularly pronounced in modified lentic ecosystems such as reservoirs which are subject to hydrological regimes (e.g., hydropeaking) that can exacerbate macrophyte-mediated impacts, including anoxic or hypoxic conditions, the related release of toxic ions (e.g., ammonia), and silt accumulation that inhibits filter-feeding. Accordingly, we compared how population size-structure and biomass of the New Zealand mussel Echyridella menziesii varied inside and outside of dense beds of invasive macrophytes known to have similar impacts on water chemistry (e.g., anoxia) in two northern New Zealand hydroreservoir locations with contrasting hydrology (lacustrine location dominated by Ceratophyllum demersum; and riverine location dominated by Egeria densa). We found adverse sediment-water interface conditions were not always associated with dense submerged macrophyte beds in littoral zones. Nonetheless, where they occurred, adverse sediment-water interface conditions were primary drivers in reduced mussel density and adult skewed size-structure, inferring reduced recruitment. Disentangling direct and indirect effects with structural equation modelling indicated that increased pore-water ammonia did not impact these primarily adult populations of freshwater mussels. Increased sediment organic matter, silt, and previously recorded hypoxia and anoxia were exacerbated in the lacustrine section where variable flows promoting water mixing were not present to reduce their effects. High densities of mussels less than 40 mm in length were associated with favourable sediment-water interface conditions of low silt and sediment organic matter, suggesting that enhanced water exchange in and around macrophyte beds may increase juvenile mussel survival in littoral zones of the riverine lake section. Our findings highlight a potential role for hydropeaking management in mitigating the development of adverse physicochemical conditions, and underscore the context-specific effects that dense non-native macrophyte beds can have on mussel populations.