The paper presents a study of annual runoff and water availability changes in the Volga–Kama and Angara–Yenisei reservoir basins under contemporary and mid-21st century scenario global anthropogenic warming. The estimates of changes are based on a comparison of runoff under global warming and for the reference period, calculated from observational data and averaged results of its calculation performed with an ensemble of global climate models. During the period of contemporary global warming, the average long-term annual runoff and water availability per unit area and per capita increased, especially in the Volga–Kama reservoir basins, with the exception of the Volgograd reservoir basin, where they decreased sharply. The observed and average model annual runoff in the considered reservoir basins is closely correlated for contemporary global warming as well as for baseline periods. However, for a fairly significant number of basins, the model runoff differs significantly from the observed value. The observed and model difference in the runoff of the two compared periods differs significantly in the Volga–Kama as well as in Angara–Yenisei reservoir basins. Nevertheless, the sign of the difference is the same in almost all basins. In 2040–2069 the annual runoff under varying intensity warming scenarios may increase relative to the model reference period runoff in all reservoir basins of the Angara–Yenisei cascade, whereas in the Volga–Kama reservoir basins the probable runoff changes are likely to have different signs relative to the runoff of the reference period. In most basins the per capita scenario water availability is likely to increase by varying degrees, partly owing to the probable population decline.