The Sao Francisco (SF) River crosses large swaths of the Brazilian semi-arid territory, and has a strategic role in the socio-economic development of northeastern Brazil. Hydroclimatic extremes (HCE) have the potential to inflict considerable social and ecological perturbations, thus a finescale spatial analysis of HCE and their trends is essential for decision-making concerning adaptive measures in the region. Trend analysis indicate that rainfall intensity increased/decreased by 10 % in 28 %/14 % of the basin during the period of 1981-2021. Parts of northern SF shows both rainfall intensification and longer dry periods, but dry conditions prevail in most of the basin. In particular, 52 % of the basin presents extended consecutive dry days. Vegetation responses to HCEs were assessed with the Normalized Difference Vegetation Index (NDVI) for the period 2001-2021, considering two contrasting land cover types: "natural vegetation" (NatVeg) and "croplands" (Crops). Correlations between NDVI and HCE indices revealed positive and significant values maximized with a lag between -1 and -3 months for both NatVeg and Crops. However, vegetation responses in singular dry and wet years showed contrasts only for the lower range of NDVI. Most of the basin show negative mean annual NDVI trends even in areas with rainfall intensification. Since NDVI showed a stronger decrease in dry episodes than increase in wet ones, it is inferred that even highly adapted vegetation such as those in the semi-arid portions of the basin face mounting challenges to recover from extended droughts exacerbated by drier year-to-year observed conditions.