Widespread losses in river connectivity and habitat degradation have led to rapid declines in migratory freshwater fishes. Large, connected tributary systems are likely critical to the conservation of fluvial species when they provide access to life-cycle-dependent habitats. The Blue Sucker (Cycleptus elongatus) is a large-bodied migratory catostomid, endemic to the large rivers of North America and declining in abundance across much of its range. Blue Suckers occupying the Wabash River (Illinois/Indiana, USA), a large tributary within the Mississippi River basin, may be one of few remaining robust populations of this species. To understand the characteristics of a successful Blue Sucker population, we analyzed data from ten years of electrofishing surveys conducted in the lower Wabash River (2010–2019, n = 563 Blue Suckers). We found Blue Sucker presence probability increased at sites with snags and with increasing surface water velocity. The length–weight regression was comparable to other populations, and the mean relative weight was 94.27. Maturation was estimated to occur at a minimum of 422 mm total length, around 2–3 years of age. We found support for variable individual spawning preparedness evidenced by inconsistent gonadal development among pre-winter adults and found support for intermittent reproductive success evidenced by a multi-modal population age structure. Genetic analysis supported the presence of a panmictic population throughout the Wabash River system, with no barrier to separate this population from the greater Mississippi River basin metapopulation. The effective population size was estimated to be 632.8 (95% CI = 318.4–4,492.2), indicating the population is not at immediate risk of inbreeding depression but should continue to be monitored. The characteristics of this resilient lower Wabash River Blue Sucker population can inform the management and conservation of this imperiled species throughout its range.