As a typical desert in the Inner Mongolia Autonomous Region, the Ulan Buh Desert has a dry climate and scarce precipitation all year round. Groundwater has become the main factor limiting the growth of vegetation in this region. It is of great significance to study the influence of groundwater depth on the spatial distribution pattern of vegetation in this region. Based on the PIE-Engine platform and using long-term time-series Landsat data, this paper analyzed the spatial–temporal distribution characteristics and trends in vegetation coverage in the Ulan Buh Desert in the last 20 years using a pixel dichotomy model and the image difference method. The Kriging interpolation method was used to interpolate the groundwater depth data from 106 monitoring wells in the Ulan Buh Desert over the past 20 years, and the spatial distribution characteristics of groundwater depth in the Ulan Buh Desert were analyzed. Finally, the correlation coefficient between changes in vegetation coverage and changes in groundwater depth was calculated. The results showed the following: (1) The vegetation coverage in the Ulan Buh Desert was higher in the periphery and lower in the center of the desert. The overall vegetation level showed an increasing trend year by year; the growth rate was 4.73%/10 years, and the overall vegetation cover showed an improving trend. (2) The overall groundwater depth in the Ulan Buh Desert was deep in the southwest and shallow in the northeast. In the past 20 years, the groundwater depth in the Ulan Buh area has become shallower, and the ecological condition has gradually improved. (3) On the whole, the vegetation coverage varied with the groundwater depth, and the shallower the groundwater depth, the greater the vegetation coverage. When the groundwater depth increased to more than 4 m, the change in the groundwater depth had a significant effect on the vegetation coverage. However, when the groundwater depth was greater than 6 m, the change in the groundwater depth had no significant effect on the change in vegetation coverage.