This research aimed to quantify and qualify alterations in land cover and verify the implications of these modifications for variables related to energy flows and water cycle in São Francisco basin (SFB), located entirely in Brazilian territory, in the second half of the 20^th century and beginning of the 21^st. For this, statistical analyzes (descriptive, trends, seasonal and correlations) were used to quantify changes in the variables of land cover and energy/water flows, in addition to relating them. As a result, it was found that the SFB lost 65,680 km² of native vegetation (10.4% of basin area) to crops and pastures, reducing water infiltration (-52%) while the rains remained stable (-2%). Water loss increased through evapotranspiration (+5%) and surface runoff (+225%). Such changes in the water cycle have entailed an 11% reduction in São Francisco river long term flow rate (Q₉₅), comparing pre and post-1990s period. In SFB, the activities that required water, such as farming activities, are those that promote hydric loss.