Hydrological regimes are significant drivers of fisheries production in many African Lakes due to their influence on fish habitat and food availability, breeding success, and catchability. Lake Turkana, Kenya, will undergo substantial changes in hydrology due to water regulation and extraction along the Omo River in neighboring Ethiopia, which provides over 90% of its water. The objective of this study was to predict how the lake's fisheries, which provide an important livelihood and protein source in the region, will respond to hydrological change. While variations in fishing effort are poor predictors of fisheries catch in the lake, water levels and their fluctuations strongly influence fisheries production. Seasonal oscillations play a particularly important role, and with complete loss of these oscillations, the lake's predicted fisheries yield will decrease by over two thirds. The fishery is predicted to collapse at a lake level decline of 25 m, regardless of seasonal amplitude magnitude. The lake's total littoral habitat, where fisheries are currently concentrated, will increase in surface area with lake level declines of <25 m. However, the extent of productive, dynamic littoral habitat will decrease with dampening of the lake's seasonal oscillations. The most severe habitat loss will occur in the lake's Turkwel Sector, which hosts the region's highest human population densities, and North Sector, where inter‐tribal conflict over resources is common and likely to be exacerbated by lake level decline. The continued ecological functioning of Lake Turkana necessitates immediate efforts to develop and apply a water resource management plan rooted in science.