Climate change is one of the most challenging and inevitable global environmental problems affecting mankind and its environment regardless of urban and rural areas. Its effect on watershed hydrology is challenging the sustainable water resources management and its availability across the globe. In order to develop a sustainable climate change adaptation strategy, understanding watershed hydrological response to the ever increasing climate change is highly important. Hence, the main objective of this study was investigating role of watershed hydrological response in developing climate resilience and adaptation strategy as a case study in Gilgal Gibe watershed, Omo Gibe river basin, Ethiopia. To achieve the main objective of the study, three regional climate models (RCM) derived from one global climate model (GCM) under two greenhouse gas emission scenarios (RCP4.5 & RCP8.5) were collected from CORDEX Africa. These data were analyzed against the 1986–2016 baseline data and projected for near future term (2020–2050) and for near future term (2051–2080). The climate dataset trend analysis over the specified period was conducted using Mann-Kendall test and the hydrological modeling was performed using the calibrated and validated HEC-HM model. From the analysis it was found that hydro-climate variability over the proposed time horizon was clearly observed from all RCM under both greenhouse gas emission scenarios. The stream flow revealed an oscillating trend over the course of the operation years under RCP4.5 and RCP8. Hence, this information is important for water resources manager, decision makers and policy makers to develop sustainable climate change resilience and adaptation.