Water availability and quality are fluctuating due to climate change, which has disastrous effects on life. Modeling climate change impact on streamflow in the Lake Tana sub‐basin (LTSB) in selected watersheds was the main goal of the research. This research is unique in that it applies the coupled MIKE SHE/MIKE HYDRO model technique, which has not been applied before to investigate changes in streamflow due to climate change in LTSB. Streamflow in the LTSB was forecasted using the MIKE SHE/MIKE HYDRO model from seven ensembles of GCMs under two emission scenarios (SSP2–4.5 and SSP5–8.5) between 2041 and 2,100. According to the calibration and validation results in the period of 1985–2007, MIKE SHE performs well while simulating streamflow in LTSB. During calibration and validation, the Nash‐Sutcliffe efficiency (NSE) values in all watersheds were greater than 0.8, except for the Ribb watershed calibration, where it was 0.75. The mean monthly changes in temperatures indicate an incremental tendency in the next decades. According to the simulation result, the monthly mean rainfall for SSP2–4.5 and SSP5–8.5 will increase from 0.05 to 61.9% and 2.02 to 46.26% in the 2050s and 8.7 to 44.38% to 6.44 to 66.24% in the 2080s, respectively. Gilgle Abay, Gumara, and Ribb watersheds will lose 56.2, 56.65, 57.01% of their mean monthly streamflow in the 2050s, according to SSP2–4.5. For the Gilgle Abay, Gumara, and Ribb watersheds, streamflow will increase by 6.7% to 21.94%, 6.08% to 23.26%, and 6.51% to 22.88%, accordingly, in the 2050s under SSP5–8.5. Increased rainfall in the watershed could result in floods in the already‐flooded Gumara and Ribb flood plains. The government and community should implement coping mechanisms to lessen the impact of climate change like early warring and planting more trees. Overall, the study showed that it is expected that conditions related to streamflow may change in the future due to climate alteration. By offering a better understanding of current and future climates, the integrated modeling system developed can assist environmentalists, hydrologists, and policymakers in water management and policy intervention.