Soil moisture is a key element of the hydrological cycle, and it significantly impacts the surface water and energy fluxes. However, a knowledge gap exists on the spatial variability of root-zone soil moisture at the regional scale in arid and hyperarid regions. Thus, soil moisture measurements at 142 sites were taken in Xinjiang (northwest China), and the relationships between soil moisture and 19 environmental factors were analyzed. The results showed that both absolute gravitational soil water content (SWC) and relative extractable water (REW) increased with increasing soil depth in the 0–100 cm soil profile. It generally decreased in the order of cropland > forestland > grassland > shrubland > bare land. Semivariograms suggested that SWC had moderate spatial dependence over a large range of 473–558 km, and REW was more randomly distributed at the regional scale in Xinjiang. Redundancy analysis suggested that environmental factors could explain 47.5%–50.9% of the variability of soil moisture, which was more strongly driven by land surface factors (p < 0.01) than by climatic factors (p > 0.05). Soil properties and other local variables explained, respectively, 40.7% and 32.3% of the variability of soil moisture in the 0–100 cm soil profile. Soil properties independently accounted for 12.8% and 28.1% of the variability in soil moisture in the 0–50 and 50–100 cm soil layers, respectively. Soil texture, field capacity, wilting point, organic carbon, bulk density, land use, and normalized difference vegetation index were the dominant factors influencing soil moisture variations.