Understanding the spatial-temporal trends and variability of vapor pressure deficit (VPD) is important for promoting climate protection and water management. This study was based on long-term series data of maximum/minimum air temperature (Tmax/Tmin) and relative humidity (RH) from 1740 meteorological stations in China from 1961 to 2020 to jointly analyze the spatial-temporal variation characteristics of VPD at different time scales, climate zones and extreme events and their influencing factor. The results showed an overall highly significant increasing trend in VPD, Tmax, and Tmin, with Sen's slope (SS) values of 0.0178 kPa/decade, 0.22 °C/decade, and 0.32 °C/decade, respectively. The opposite was true for RH (SS = −0.41%/decade). Moreover, the trends all changed abruptly around the year 2000. The VPD exhibited a highly significant upward trend in spring as well as at the junction of climatic zones and along the southeastern coast. This was particularly evident in the semi-arid steppe of Inner Mongolia (IM), the humid tropical south China (SC), and the semi-humid warm-temperate north China (NC) regions. For the frequency distribution of VPD extremes in each climate zone, the arid desert of northwest China (NWC)> > IM > NC. The frequency range was 758–910 days/decade, 249–410 days/decade, and 170–300 days/decade, respectively. Moreover, their average frequency of extreme events was 88 times/decade, 55 times/decade, and 38 times/decade respectively. The main meteorological factors affecting VPD taken together were Tmax, RH, Tmin, sunshine duration (N), and wind speed (U2) with mean importance values of 0.612, 0.351, 0.020, 0.016, and 0.001 respectively. Meanwhile, we found that VPD and reference crop evapotranspiration (ET0) were positively correlated and negatively correlated with soil water content and altitude. The maximum growth rate of VPD was observed in Cropland and Impervious environments. This research reveals the spatial-temporal characteristics of meteorological elements in China and provides a reference for scholars to formulate countermeasures against climate change.