Having an extreme topography and heterogeneous climate, the Upper Indus Basin (UIB) is more likely to be affected by climate change and it is a crucial area for climatological studies. Based on the monthly minimum temperature (T_min), maximum temperature (T_max) and precipitation from nine meteorological stations, the spatiotemporal variability of temperature and precipitation were analyzed on monthly, seasonal, and annual scales. Results show a widespread significant increasing trend of 0.14 °C/decade for T_max, but a significant decreasing trend of −0.08 °C/decade for T_min annually, during 1955–2016 for the UIB. Seasonally, warming in T_max is stronger in winter and spring, while the cooling in T_min is greater in summer and autumn. Results of seasonal T_max indicate increasing trends in winter, spring and autumn at rates of 0.38, 0.35 and 0.05 °C/decade, respectively, while decreasing in summer with −0.14 °C/decade. Moreover, seasonal T_min results indicate increasing trends in winter and spring at rates of 0.09 and 0.08 °C/decade, respectively, while decreasing significantly in summer and autumn at rates of −0.21 and −0.22 °C/decade respectively for the whole the UIB. Precipitation exhibits an increasing trend of 2.74 mm/decade annually, while, increasing in winter, summer and autumn at rates of 1.18, 2.06 and 0.62 mm/decade respectively. The warming in T_max and an increase in precipitation have been more distinct since the mid-1990s, while the cooling in T_min is observed in the UIB since the mid-1980s. Warming in the middle and higher altitude (1500–2800 m and >2800 m) are much stronger, and the increase is more obvious in regions with elevation >2800 m. The wavelet analysis illustrated sporadic inter-annual covariance of seasonal T_max, T_min and precipitation with ENSO, NAO, IOD and PDO in the UIB. The periodicities were usually constant over short timescales and discontinuous over longer timescales. This study offers a better understanding of the local climate characteristics and provides a scientific basis for government policymakers.