Research has confirmed that the global terrestrial vapor pressure deficit (VPD) has already increased and will continue to increase. In this context, it is worth exploring whether the atmospheric environment in Xinjiang of China tends to be drier. The VPD series of Xinjiang from 1961 to 2020 was calculated based on meteorological observation data. Then, the distribution and spatio-temporal evolution characteristics of VPD were studied by linear trend analysis, Mann-Kendall test, etc. The results are as follows: (1) From 1982 to 2015, the average annual VPD in Xinjiang exhibited an obvious upward trend with an increased rate of 0.015 kPa·(10a)^-1. As shown in the Mann-Kendall test, an abrupt change in VPD occurred around 2005, and a weakly fluctuating change was observed before the mutation, followed by an increasing trend. (2) There were significant differences in the intensity of VPD in different seasons, but increasing trend changes, even though the rates of increase differed, which appeared in the series of mean VPD values for each season. In comparison, the magnitude of increase in VPD sequences was greater in spring and summer and the smallest in winter. The characteristics of abrupt changes in VPD sequences in spring and autumn were relatively consistent with the changes in the annual VPD value series, whereas summer was slightly later, with the abrupt change that occurred in 2006. (3) Spatially, VPD exhibited a distinct difference of “low in the mountains and high in the basins”, and there was spatial heterogeneity in its long-term evolution trend. A large area of the entire territory (approximately 83.65% of the meteorological stations) exhibited an increasing trend in VPD, whereas the stations with decreasing trends were mostly distributed in the northern foothills of the eastern part of the Tianshan Mountains and the northern/northwestern edge of the south Xinjiang Basin. On the seasonal scale, the number of meteorological stations with increasing trend changes in VPD in spring accounted for the highest proportion of the total number of stations (96.15%), indicating that this season is the most extensive period of VPD in Xinjiang. Comparatively, the relatively small variation of the VPD time series showed that the atmospheric dryness during winter in Xinjiang was relatively stable in the long term. This study reveals the evolution of VPD in Xinjiang under a significant shift from warm-wet to warm-dry and serves as a reference for reducing uncertainties in the prediction of changes in ecosystem structure and function.