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Climate change has been intensifying droughts throughout Pakistan’s essential water source region, the Upper Indus River Basin (UIRB). This study evaluates spatiotemporal drought patterns (1982–2014) using SPI and SPEI at 1- to 12-month scales across 11 stations. SPEI demonstrates superior performance over SPI when detecting droughts produced by temperature variations, since it shows better accuracy of 20 to 30%. Results indicate that northern high-altitude regions, including Astore and Dir, experience worsening drought conditions because we use rainfall as precipitation so the regions which have low rainfall are demonstrate drought areas in this study. The Modified Mann-Kendall test shows central and northern parts of UIRB are drying out, as demonstrated by Astore’s SPEI-12 dropping at a rate of −0.35 decade⁻¹. The Modified Mann-Kendall test shows significant drying patterns throughout central/northern UIRB, where Astore experienced SPEI-12 declines equal to -0.35 decade⁻¹. Precipitation prediction achieves better accuracy when using Multivariable Linear Regression instead of Partial Least Squares Regression (PLSR) because its RMSE value is slightly lower, and it reveals that temperature and longitude are vital predictors. The number of drought occurrences from 2001 to 2014 at Mangla Reservoir reached 54 events, while it remained at 9 events from 1982 to 1990. The UIRB remains susceptible to drought conditions caused by rising temperatures, thus requiring SPEI-based monitoring systems to implement adaptive water resource management practices. The framework applies to mountainous basins worldwide when fighting droughts that result from climate change.