Results emphasise the importance of the spatial variation in runoff sensitivity. Due to the MDB’s aridity, basin-average runoff is very low (around 28 mm y−1) and runoff is generally insensitive to changes in average precipitation and potential evaporation. Specifically, basin-wide runoff is expected to increase by 1 mm y−1 for a 10 mm y−1 increase in basin-average precipitation, and to remain unchanged for the same increase in potential evaporation. However, approximately 66 % of basin flow originates from 12 % of the basin’s land area and in these few high yield catchments runoff is most sensitive to changes in climatic conditions. In the highest yield zone, runoff is expected to increase by 7 mm y−1 given a 10 mm y−1 increase in precipitation, and to decrease by around 4 mm y−1 for the same increase in potential evaporation. When applied spatially, this runoff sensitivity framework has the potential to help water managers and policy makers to target planning activities that seek to mitigate potential effects of a changing climate on water resources.