The increasing drought frequency poses a significant threat to global and regional river systems and ecosystem functioning, especially in the complex topographical Buffalo River catchment area of the Eastern Cape Province, South Africa. This study explored the impact of drought on riparian vegetation dynamics using the Normalize Difference Vegetation Index (NDVI), Transformed Difference Vegetation Index (TDVI) and Modified Normalized Difference Water Index (MNDWI) from satellite-derived Landsat data from 1990 to 2020. The least-squares linear regression and Pearson’s correlation coefficient were used to evaluate the long-term drought in riparian vegetation cover and the role of precipitation and streamflow. The correlation results revealed a moderate positive correlation (r = 0.77) between precipitation and streamflow with a significant p-value of 0.04 suggesting consequences on riparian vegetation health. Concurrent with the precipitation, the vegetation trends showed that precipitation increased insignificantly with less of an influence while the reverse was the case with the streamflow in the long term. The results show that the NDVI and TDVI were significant indices for detecting water-stressed vegetation in river catchment dynamics. Much of these changes were reflected for MNDWI in dry areas with a higher accuracy (87.47%) and dense vegetation in the upper catchment areas. The standardized precipitation index (SPI) revealed the inter-annual and inter-seasonal variations in drought-stressed years between 1991–1996, 2000–2004, 2009–2010, 2015, and 2018–2019, while 2020 exhibited slight sensitivity to drought. The findings of this study underscore the need for heightened efforts on catchment-scale drought awareness for policy development, programs, and practices towards ecosystem-based adaptation.