Under global warming, flooding has become one of the most destructive natural disasters along the China–Pakistan Economic Corridor (CPEC), which significantly jeopardizes the construction and ongoing stability of the CPEC. The assessment of regional flood potential is, therefore, crucial for effective flood prevention and relief measures. In light of this, our study applied MIKE 11 hydrodynamic model for the Indus River Basin of Pakistan to achieve a comprehensive analysis of the flood-affected locations and depths under typical scenarios. The flood risk zones along the CPEC were evaluated using the indicator system method in conjunction with the combination weighting method. The results show that the hydrodynamic model has a Nash–Sutcliffe efficiency of 0.86, allowing for the investigation of floods at more precise temporal and spatial scales. Punjab, Sindh, and Balochistan Provinces are the main inundation areas under a 100-year flood scenario, with inundation depths ranging from 1 to 4 m. The coastal regions of Sindh and Hafizabad in Punjab witnessed the most severe floods, with maximum inundation depths exceeding 8 m. Flooding predominantly impacts the southeastern region of the CPEC. The medium- to high-risk zones comprise 25.56% of the region, while high-risk areas constitute 4.18%. Particularly, the eastern and southern regions of Punjab, along with the central and southern regions of Sindh, have been pinpointed as high-risk areas, primarily due to their dense population and riverine characteristics. Overall, our findings provide a scientific basis for informed decision making pertaining to disaster reduction and flood prevention.