Quantifying drought and wetness fluctuations is of great significance to the regional ecological environment and water resource security, especially in the fragile Qinghai-Tibetan Plateau (QTP). In this paper, the standardized precipitation evapotranspiration index (SPEI) was calculated based on the observed data and China Meteorological Forcing Dataset (CMFD) in the QTP for the period of 1979–2015, and the drought and wetness evolution based on the SPEI series and respective contribution of temperature and precipitation were also analyzed. Results indicated that meteorological stations are mainly concentrated in the eastern part of the plateau, which cannot reflect the drought and wetness trend of the whole QTP. The linear trend and Mann–Kendall test revealed that SPEI series calculated based on CMFD data at 1-, 3-, 6-, 9-, 12-, and 24-month time scales all showed significant upward trend
p
<
0.01
, indicating that the QTP as a whole tended to be wetter. Spatially, the regions with significant drying
p
<
0.1
and increased drought probability were mainly concentrated in the Qaidam Basin and the southern part of the QTP, and the mean contribution rates of temperature and precipitation variability to SPEI trend in these regions were 60% and −11%, respectively. The regions with significant wetting
p
<
0.1
and decreased drought probability were mainly concentrated in the northeast, central, and western parts of the plateau, and the mean contribution rates of temperature and precipitation variability to SPEI trend were −9% and 61% in these regions. From the statistics in different climatic regions, most of the arid and humid regions in the QTP tended to be drier, while the semiarid regions tended to be wetter.