The Devils Hole pupfish is an icon of desert fishes conservation and management in the United States. Nonetheless, after over 50 years of management, the wild population remains critically endangered due to its very small, nutrient-limited, and seiche-prone habitat in combination with its long-term small population size leading to reduced genetic health of the population. There remains a diabolical tension in understanding how the rapidly changing infernal environment of Devils Hole and the fiendishly low genetic diversity of this species are impacting its long-term prospects of survival. Here we directly assess the genetic health of this species by constructing the first de novo genome assembly and sequencing 186 whole genomes of Death Valley pupfishes, including over 50 Devils Hole pupfish. We also reconstructed a historical timeline of genetic diversity from museum samples and sequenced embryos that prematurely died during development. We estimated genetic diversity in Devils Hole pupfish to be among the lowest measured in any wild species which has persisted at this low level since at least the 1940’s before the most intense periods of anthropogenic disturbance. The wild population contained about twice the genetic diversity of the Ash Meadows Fish Conservation Facility refuge population in 2020, despite annual introductions of wild fish to the refuge. We also show that the most inbred individuals in the population with approximately half of their DNA in runs of homozygosity inherited from a recent common ancestor due to inbreeding are 9 times more likely to die prematurely during embryonic development than individuals with only 10% in identical runs. Our comprehensive analyses of genomic health in this species should provide a strong foundation for future management actions in addition to highlighting the ability of this iconic endangered species to provide insights into broader evolutionary theory.