The Three Rivers` Headwaters region is significant and sensitive to climate change, facing with climate change that characterized as “warming and wetting”. From perspectives of spatial pattern, climate extreme indices and comparison among regional-global climate variations, we investigated the characteristics of climate variations and climate extremes in the Three Rivers` Headwaters region over the Tibetan Plateau from 1961 to 2019. Temperature and precipitation observations are obtained from 20 meteorological stations of China Meteorological Administration and HadCRUT4 as well as NOAA Precipitation Reconstruction datasets. It is revealed that the spatial averaged warming rate is 0.37 °C/10a, which has been more than the global level (0.16 °C/10a) during the nearly past 60 years, which is also significantly higher than the same latitude (0.19 °C/10a) and China region (0.28 °C/10a). Under the background of climate warming, most of the extreme climate indices in the Three Rivers` Headwaters region have risen, and the most significant rise is night extreme high temperature (0.55 °C/10a), suggesting the extremeness of regional climate has increased. The spatial pattern of temperature and precipitation during the nearly past 60 years possesses a positive gradient along the northwest-southeast direction, and its changing trend is characterized by the spatial differentiation of warming and humidification with a rising rate from west to east. Furthermore, the temporal-spatial patterns of climate change and climate extremes in the Three Rivers` Headwaters region can provide a conclusive basis for the research on the vulnerability of climate systems and ecosystems in this region. At the same time, this study also provides a comparative case for studies on the response of climate -sensitive alpine regions to global warming.