Abstract: Temporary plugging fracturing of horizontal wells is the key to improving the stimulation results of unconventional reservoirs. The accurate prediction of the migration and plugging characteristics of the ball sealer in horizontal wells plays a prominent role in the successful implementation of the temporary plugging and fracturing of horizontal wells. Therefore, it is necessary to employ numerical simulation methods to simulate the migration and plugging characteristics of ball sealer in horizontal wells. Since the coupled CFD-DEM model can treat the ball sealer as a rotating sphere and accomplish two-way coupling between particle and fluid, a numerical model of wellbore temporary plugging in horizontal shale gas wells was established based on the CFD-DEM coupling method to analyze the influence of ball sealer diameter, fracturing pump rate, and ball sealer density on the migration and sealing behavior of ball sealers. The results showed that for a casing diameter of ϕ139.7 mm, with a single-cluster and a 8-perforation spiral distribution, the effect of wellbore temporary plugging was the best when the ratio of perforation diameter to ball sealer diameter was about 0.97. The sealing efficiency of the ball sealer first increased and then decreased with the increase of pump rate. When the pump rate was less than 6 m³/min, the sealing efficiency of the ball sealer increased with the increase in the pump rate. When the pump rate was 4–7 m³/min, the sealing efficiency of the ball sealer was higher. The low-density ball sealer had the highest sealing efficiency, and the high-density ball sealer had the lowest sealing efficiency. In addition, the ball sealer was most likely to seal the perforation in the second half interval of the perforation cluster or the first perforation. The temporary plugging model of horizontal shale gas wells based on CFD-DEM coupling can provide a visualization of the migration process of the ball sealer in the horizontal section and predict the migration speed of the ball sealer and the position of the sealed perforation, which provides a guideline for the temporary plugging fracturing design and field implementation in horizontal wells.