In this study, scenarios of changes in land-use patterns, agricultural production and climate, and their effects on water demand and availability in the São Francisco river basin (Brazil) are analysed. The global driver population growth, economic development, and trade liberalization are included. Using the regionalized version of a global agro-economic land-and water use model, impacts are analysed for two scenarios: a regionalized world with slow economic development, high population growth, and little awareness of environmental problems (A2), and a globalized world with low population growth, high gross domestic product (GDP) growth, and environmental sustainability (B1). A regional ecohydrological model is used to analyse the effect of these scenarios on water demand and availability. The climate scenarios in general show a wetter future (years 2021–2050), with wetter rainy seasons and drier dry seasons. The water availability for irrigated agriculture is high, while hydropower generation is declining by 3.2%(A2) and 1.7%(B1) compared to the reference.