Hydroclimatic extremes such as droughts and floods triggered by human-induced climate change are causing severe damage in the Nile River Basin (NRB). These hydroclimatic extremes are not well studied in a holistic approach in NRB. In this study, the Gravity Recovery and Climate Experiment (GRACE) mission and its Follow on mission (GRACE-FO) derived indices and other standardized hydroclimatic indices are computed for developing monitoring and evaluation methods of flood and drought. We evaluated extreme hydroclimatic conditions by using GRACE/GRACE-FO derived indices such as water storage deficits Index (WSDI); and standardized hydroclimatic indices (i.e., Palmer Drought Severity Index (PDSI) and others). This study showed that during 1950–2019, eight major floods and ten droughts events were identified based on standardized-indices and GRACE/GRACE-FO-derived indices. Standardized-indices mostly underestimated the drought and flood severity level compared to GRACE/GRACE-FO derived indices. Among standardized indices PDSI show highest correlation (r2 = 0.72) with WSDI. GRACE-/GRACE-FO-derived indices can capture all major flood and drought events; hence, it may be an ideal substitute for data-scarce hydro-meteorological sites. Therefore, the proposed framework can serve as a useful tool for flood and drought monitoring and a better understanding of extreme hydroclimatic conditions in NRB and other similar climatic regions.