Soil moisture (SM), an important variable in water conversion between the atmosphere and terrestrial ecosystems, plays a crucial role in ecological processes and the evolution of terrestrial ecosystems. Analyzing and exploring SM’s processes and influencing factors in different permafrost regions of the Qinghai-Tibet Plateau (QTP) can better serve the regional ecological security, disaster warning, water management, etc. However, the changes and future trends of SM on the QTP in recent decades are uncertain, and the main factors affecting SM are not fully understood. The study used SM observations, the Global Land Evapotranspiration Amsterdam Model (GLEAM) SM products, meteorological and vegetation data, Mann–Kendall test, Theil–Sen estimation, Ensemble Empirical Mode Decomposition (EEMD), and correlation methods to analyze and explore the characteristics and influencing factors of SM change in different permafrost regions of the QTP. The results show that: (1) At the pixel scale, GLEAM SM products can better reflect SM changes in the QTP in the warm season. The seasonal permafrost region is closer to the real SM than the permanent region, with a median correlation coefficient (R) of 0.738, median bias of 0.043 m3 m−3, and median unbiased root mean square errors (ubRMSE) of 0.031 m3 m−3. (2) The average SM in the QTP warm season increased at a rate of 0.573 × 10−3 m3 m−3 yr−1 over the recent 40 years, and the trend accelerated from 2005–2020. In 64.31% of the region, the soil was significantly wetted, mainly distributed in the permafrost region, which showed that the wetting rate in the dry region was faster than in the wet region. However, the wetting trend does not have a long-term continuity and has a pattern of “wetting–drying-wetting” on interannual and decadal levels, especially in the seasonal permafrost region. (3) More than 65% of the SM wetting trend on the QTP is caused by temperature, precipitation, and vegetation. However, there is apparent spatial heterogeneity in the different permafrost regions and vegetation cover conditions, and the three factors have a more substantial explanatory power for SM changes in the seasonal permafrost region. With the global climate change, the synergistic SM–Climate–Vegetation effect on the QTP tends to be more evident in the seasonal permafrost region.