Impacts of invasive species are most often evaluated locally and shortly after establishment, yet far fewer studies examine how impacts spread and vary as invaders persist and expand across space and time. The non-native Asian swamp eel (Monopterus albus/javanensis) has been established in the relatively small (<250 km²) Taylor Slough drainage of the freshwater Everglades (FL) for 12-16 years, where it has reduced or collapsed (>90%) several fish and crayfish populations. The eel has now spread throughout much of the remaining 6000 km² ecosystem, including larger drainages, seasonally drying marshes, and wetlands with less depth fluctuation. We used long-term monitoring datasets (1996-present) of small native marsh fishes and decapods to quantify invasive eel impacts in three additional regions with contrasting hydrologic regimes and species compositions. For more permanent slough regions, we fitted baseline species–hydrology models for dominant fishes and decapods using pre-invasion data (Shark River Slough < 2021; Water Conservation Area < 2017). Invasion impacts were assessed using Monte Carlo randomization to test whether post-invasion residual deviations exceeded those expected from pre-invasion variability. Prey responses were spatially heterogeneous and weaker in the region with least hydrologic variability. Most, but not all native fish species exhibited substantial density declines relative to expectations in one or both slough regions (mean loss = 46.4%), ranging from moderate reductions for bluefin killifish (L. goodei; −16.6%) to local extirpations of flagfish (J. floridae). Slough crayfish (P. fallax) declined by an average of 59.8%, whereas grass shrimp (P. paludosus) occasionally exceeded expected densities(+87.1% in Shark River Slough). Using a Before-After-Control-Impact approach and a reference region far west of the invasion, we even found evidence for 41% reductions in crayfish densities (P. alleni) in shallower seasonally drying marshes (Impact*Post = −0.46, p = 0.039). Several species responses were consistent with patterns reported from the region of first invasion, while magnitudes were somewhat smaller. Our results demonstrate that invasion impacts can emerge as diffuse spreading processes that progressively erode prey populations with some variability among systems. Accounting for continued invasion dynamics is therefore essential for understanding freshwater ecosystem resilience and anticipating long-term consequences of persistent non-native species.