Human water use combined with a recent megadrought have reduced river and stream flow through the Southwestern United States and led to periodic drying of formerly perennial river segments. Reductions in snowmelt runoff and increased extent of drying collectively threaten short-lived, obligate aquatic species, including the endangered Rio Grande silvery minnow. This species experiences ‘boom-and-bust’ population dynamics where large fluctuations in abundance are expected to lower estimates of effective population size and erode genetic diversity over time. Rates of diversity loss are also affected by additions of hatchery-origin fish used to supplement the wild population. We leveraged demographic and genetic data from wild and hatchery individuals to understand the relationship of genetic diversity and effective population size to abundance over the last two decades. Genetic diversity was low during the early 2000s, but diversity and demographic metrics stabilized after the hatchery program was initiated and environmental conditions improved. Yet, from 2017 onward, allelic diversity declined (Cohen's d = 1.34) and remains low despite hatchery stocking and brief wild population recovery. Across the time series, single-sample estimates of effective population size (N_eD) were positively associated (r = 0.53) with wild/total abundance, but as the proportion of hatchery-origin spawners increased, N_eD was reduced (r = -0.55). Megadrought limits wild spawner abundance and precludes refreshment of hatchery brood stocks with wild fish, hence we predict a riverine population increasingly dominated by hatchery-origin individuals and accelerated loss of genetic diversity despite supplementation. We recommend an adaptive and accelerated management plan that integrates river flow management and hatchery operations to slow the pace of genetic diversity loss exacerbated by megadrought.