Recent evidence of regional climate change impacts on hydrological cycle directed us to study the floods in a high elevated and rapidly urbanized river basin, the Kabul River basin (KRB), Pakistan, which is susceptible to frequent flooding. Therefore, we analyzed the changes in flood regime at various spatial and temporal scales and their possible causes, which is accomplished by using flood indicators, trend analysis, change point analysis, and hydrological modeling. The results showed that the northern and northwestern parts of the KRB were more exposed to flood hazard than the southern parts under long-term scenario (1961/64-2015). However, after the change points, the flood risk decreased in the northern and increased in the southern regions. This spatial shift increased the vulnerability of population to the flood hazard, because the majority of population resides in the southern region. The extreme precipitation has also increased, especially the maximum one-day rainfall and maximum five-day rainfall throughout the basin. Particularly, the major cause of the decrease in different flood indicators in the northern parts of the KRB is the corresponding decrease in the annual and monsoonal rainfall and corresponding positive mass balance of glaciers in the northern region after the occurrence of change point in flood regime. However, the major cause of the increase in flood hazard on the southern part of the KRB is associated with maximum five-day rainfall. A 68% variability of annual maximum flood for the Kabul River at Nowshera and an 84% variability of annual maximum flood for Bara River at Jhansi post are explained by maximum five-day rainfall. In addition, a considerable decrease in forests (–5.21%) and increase in the urban area (88.26%) from 1992–2015 also amplifies the risk of higher flood peaks. The results of hydrological modeling suggest that the six-hourly flood peak increased by 6.85% (1992–2010) and 4.81% (2010–2015) for the extreme flood of 2010 for the Kabul River at Nowshera. The flood peak per decade will increase by 8.6%, as compared to the flood peak under the land use scenario of 2010. Therefore, consideration of proper land use planning is crucial for sustainable flood management in the KRB.