Fishes of the Truckee River basin (California and Nevada) evolved in an aquatic system that has been episodically diminished by extended drought. For potamodromous species, such as the endangered Cui-ui endemic to Pyramid Lake, Nevada, prehistoric episodic severe drought presumably led to periods of failed reproduction due to restricted access to spawning habitat. The response of the Cui-ui population to more recent failed reproduction caused by anthropogenic activity was studied to learn how to manage this species through periods of spawning disruption. Adult Cui-ui survival averaged 91% and 89% for females and males, respectively, in drought years when spawning migrations were either precluded or few fish migrated because of no or low stream flow. In each of 2 years when stream access was precluded, the adult survival was nearly 100% suggesting that Cui-ui survival is extended in the absence of a spawning migration. Survival averaged 62% and 60% for females and males, respectively, in years of spawning migrations. Strong predominant year-classes developed in the year immediately following a period of failed reproduction, indicating the species’ capacity for population rebound. Year-class predominance persisted for 6–10 years and through years of low survival associated with migration years, and this predominance is probably due, in part, to a diverse age at maturity. Contemporary water diversions from the Truckee River provided the opportunity to study the response of the Cui-ui population to years of failed reproduction. A projected drier Truckee River basin associated with global climate change will test the Cui-ui’s adaptive capacity to endure periods of reproductive failure. This study is aimed at assisting Cui-ui managers in conserving the species in this highly regulated and changing system. The study also adds insight into the prehistoric population dynamics of a potamodromous species in the arid western United States subject to wide fluctuations in annual precipitation and water availability.