Largely depending on meltwater from the Hindukush–Karakoram–Himalaya, withdrawals from the upper Indus basin (UIB) contribute to half of the surface water availability in Pakistan, indispensable for agricultural production systems, industrial and domestic use and hydropower generation. Despite such importance, a comprehensive assessment of prevailing state of relevant climatic variables determining the water availability is largely missing. Against this background, we present a comprehensive hydro-climatic trend analysis over the UIB, including for the first time observations from high-altitude automated weather stations. We analyze trends in maximum, minimum and mean temperatures (Tx, Tn, and Tavg, respectively), diurnal temperature range (DTR) and precipitation from 18 stations (1250–4500 m a.s.l.) for their overlapping period of record (1995–2012), and separately, from six stations of their long term record (1961–2012). We apply Mann–Kendall test on serially independent time series to assess existence of a trend while true slope is estimated using Sen's slope method. Further, we statistically assess the spatial scale (field) significance of local climatic trends within ten identified sub-regions of UIB and analyze whether the spatially significant (field significant) climatic trends qualitatively agree with a trend in discharge out of corresponding sub-region. Over the recent period (1995–2012), we find a well agreed and mostly field significant cooling (warming) during monsoon season i.e. July–October (March–May and November), which is higher in magnitude relative to long term trends (1961–2012). We also find general cooling in Tx and a mixed response in Tavg during the winter season and a year round decrease in DTR, which are in direct contrast to their long term trends. The observed decrease in DTR is stronger and more significant at high altitude stations (above 2200 m a.s.l.), and mostly due to higher cooling in Tx than in Tn. Moreover, we find a field significant decrease (increase) in late-monsoonal precipitation for lower (higher) latitudinal regions of Himalayas (Karakoram and Hindukush), whereas an increase in winter precipitation for Hindukush, western- and whole Karakoram, UIB-Central, UIB-West, UIB-West-upper and whole UIB regions. We find a spring warming (field significant in March) and drying (except for Karakoram and its sub-regions), and subsequent rise in early-melt season flows. Such early melt response together with effective cooling during monsoon period subsequently resulted in a substantial drop (weaker increase) in discharge out of higher (lower) latitudinal regions (Himalaya and UIB-West-lower) during late-melt season, particularly during July. These discharge tendencies qualitatively differ to their long term trends for all regions, except for UIB-West-upper, western-Karakorum and Astore. The observed hydroclimatic trends, being driven by certain changes in the monsoonal system and westerly disturbances, indicate dominance (suppression) of nival (glacial) runoff regime, altering substantially the overall hydrology of UIB in future. These findings largely contribute to address the hydroclimatic explanation of the "Karakoram Anomaly".