Five watersheds (W1, W2, W3, W4 and W5) in the upper Indus basin were chosen for detailed studies to understand the influences of geomorphology, drainage basin morphometry and vegetation patterns on hydrology. From the morphometric analysis, it is evident that the hydrologic response of these watersheds changes significantly in response to spatial variations in morphometric parameters. Results indicate that W1, W2 and W5 contribute higher surface runoff than W3 and W4. Further, the topographic and land cover analyses reveal that W1, W2 and W5 generate quick runoff that may result in flooding over prolonged rainy spells. A physically based semi-distributed hydrologic model (soil and water assessment tool, SWAT) was used for simulating the hydrological response from the watersheds. As per the simulations, W5 watershed produces the highest runoff of 11.17 mm/year followed by W1 (7.9 mm/year), W2 (6.6 mm/year), W4 (5.33 mm/year) and W3 (4.29 mm/year). Thus, W5 is particularly more vulnerable to flooding during high rain spells followed by W1, W2, W4 and W3, respectively. Synthetic unit hydrograph analysis of the five watersheds also reveals high peak discharge for W5. The simulated results on the hydrological response from the five watersheds are quite in agreement with those of the morphometric, topographic, vegetation and unit hydrograph analyses. Therefore, it is quite evident that these factors have significant impact on the hydrological response from the watersheds and can be used to predict flood peaks, sediment yield and water discharge from the ungauged watersheds.