Although the effects of climate warming on the chemical and physical properties of lakes have been documented, biotic and ecosystem-scale responses to climate change have been only estimated or predicted by manipulations and models. Here we present evidence that climate warming is diminishing productivity in Lake Tanganyika, East Africa. This lake has historically supported a highly productive pelagic fishery that currently provides 25-40% of the animal protein supply for the populations of the surrounding countries. In parallel with regional warming patterns since the beginning of the twentieth century, a rise in surface-water temperature has increased the stability of the water column. A regional decrease in wind velocity has contributed to reduced mixing, decreasing deep-water nutrient upwelling and entrainment into surface waters. Carbon isotope records in sediment cores suggest that primary productivity may have decreased by about 20%, implying a roughly 30% decrease in fish yields. Our study provides evidence that the impact of regional effects of global climate change on aquatic ecosystem functions and services can be larger than that of local anthropogenic activity or overfishing.