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• Fine scale processes are represented well by high resolution of the RegCM4.3. • Spatial patterns of precipitation were simulated well by RegCM4.3 over the NUIB. • Significant alteration in mean monthly flow was found in the post-monsoon season. • The monsoon precipitation events will occur with high frequency over the NUIB. • The NUIB is expected to be confronting with more floods by the end of 21st century. In the present research, we used bias corrected output of regional climate model (RegCM4.3) to generate streamflow for future climate change projections in the Northwestern Upper Indus Basin (NUIB) under RCP4.5 and RCP8.5 scenarios. The average annual runoff was found to be continuously increasing by the end of 21st century. The increase in precipitation as well as the streamflow for summer and winter in the NUIB indicated that RegCM4.3 simulated climate change projections were realistically transferred to HEC-HMS hydrological model. Maximum streamflow peaks, both in frequency and magnitude, were observed in July and August over three streamflow gauges (i.e. Besham, Nowshera and Khairabad) posing possible threats of flood risks during the monsoon season in Pakistan. Significant streamflow changes were projected for winter and spring seasons. The analysis of flow duration curve for three hydrometric stations indicates that the flow occurrence probability could be greater under both scenarios relative to the reference period. The increase in streamflow was projected under high (Q 5) and medium (Q 50) flow, which could possibly be related with the increase in monsoon precipitation events in the NUIB. Overall it is to be expected that the NUIB will confront more floods as a result of projected increase in medium and high flow, which demands better policies and management towards the water resources of the NUIB. This study is expected to contribute considerably to climate change impact assessment studies over the NUIB, Pakistan. [ABSTRACT FROM AUTHOR]