Precipitable Water Vapor (PWV) constitutes a pivotal parameter within the domains of atmospheric science, and remote sensing due to its profound influence on Earth's climate dynamics and weather patterns. It exerts a significant impact on atmospheric stability absorption and emission of radiation, thus engendering alterations in the Earth's radiative equilibrium. As such, precise quantification of PWV holds the potential to enhance weather prognostication and fortify preparedness against severe meteorological phenomena. This study aimed to elucidate the spatial and temporal changes in seasonal and annual PWV across the Indus River Basin and its sub-basins using ERA5 reanalysis datasets. The present study used ERA5 PWV (entire atmospheric column), air temperature at 2 m (t2m) and 500 hPa (T_500hPa), evapotranspiration, and total cloud cover data from 1960 to 2021. Theil Sen slope estimator and Mann-Kendall test were used for trend analysis. Correlation and multiple regression methods were used to understand the association of PWV with other factors. The findings have unveiled the highest increase in mean PWV during the monsoon (0.40 mm/decade), followed by pre-monsoon (0.37 mm/decade), post-monsoon (0.27 mm/decade), and winter (0.19 mm/decade) throughout the study period. Additionally, the mean PWV exhibited the most pronounced positive trend in the sub-basin Lower Indus (LI), followed by Panjnad (P), Kabul (K), and Upper Indus (UI) across all seasons, except winter. Annual PWV has also risen in the Indus basin and its sub-basins over the last six decades. PWV exhibits a consistent upward trend up to an elevation of 3500 m within the basin which is most pronounced during the monsoon season, followed by the pre-monsoon. The escalating PWV within the basin is reasonably ascribed to increasing air temperatures, augmented evapotranspiration, and heightened cloud cover. These findings hold potential utility for pertinent authorities engaged in water resource management and planning.