During the past few decades, significant climatic and hydrologic changes have occurred across the Qinghai-Tibet Plateau (QTP) due to global climate change. The characteristics of wetness and dryness can reflect changes in moisture and climate, and studying these from the perspective of climate change are important for revealing the response of the regional environment to climate change and to the problems of ecohydrological evolution. Wetness/dryness variations and spatiotemporal characteristics of the potential evapotranspiration rate (PER) in the Three-River Headwaters region (TRH) were analyzed using the Holdridge life zone model based on daily hydrological and meteorological data for the period 1957-2014. The Pettitt test, accumulated anomaly, and linear trend were used to detect the change point and long-term variation trend of PER and other factors during the period, respectively. Inverse distance weighting (IDW) was used to analyze the spatial distribution and change characteristics of PER, and a regression analysis was used to estimate the contribution rates of the meteorological factors to the change in PER. We then discussed the variations in meteorological elements that influenced wetness and dryness from the perspective of climate change. The results of these analyses are as follows:(1) Temporally, the PER of the TRH region significantly increased (P < 0.05), and the change point was found to occur in 1997 (P < 0.1). The PER exhibited a relatively slow decline during 1957-1997 and then rose in the 1970s-1980s. Finally, a drying trend intensified after 1998. (2) Spatially, the mean annual PER decreased southeast-to-northwest, and the annual PER recorded at most stations increased, while the growth rates in the north and southwest were relatively slow. (3) The PER were correlated positively with precipitation and relative humidity, correlated negatively with air temperature and sunlight. Among the influences mentioned above, temperature was the main natural factor that influences the wetness/dryness changes. According to the results of an attribution analysis, PER was primarily influenced by air temperature and wind speed, which had contribution rates of 48% and 42%, respectively, but the contribution of wind speed was not significant. Thus, it was concluded that rising temperature was the main factor related to warming and drying in the TRH region during 1957-2014. This study suggests that the Holdridge life zone model can be utilized to evaluate the characteristics of wetness and dryness in the TRH region. An analysis of warming and drying impacts on the hydrological and ecological environment showed that ecological problems caused by drying, such as soil water-thermal characteristics and hydrologic regime changes, vegetation degradation, wetland shrinkage and loss of biodiversity amongst others, are intensified. To slow down the effects of drought, a series of protection measures should be carried out, for instance, reducing human intervention, increasing pastures, assigning importance to the protection of biodiversity, modifying the weather in suitable areas, and filling reservoirs to protect water sources.