The drag coefficient (CD) for particles has a significant effect on the gas–solid fluidization characteristics. However, it is unclear whether the particle surface roughness (Rap) can notably affect CD at relatively low particle Reynolds numbers (Rep). Herein, the CD for several single near-spherical particles with different Rap and density were determined using high-speed videography in conjunction with the image analysis method. In addition, a quasi-direct numerical simulation (q-DNS) method was applied to further resolve the flow field surrounding the particle. Both experimental and simulation results suggest that within a low Rep range (<500), there is no evident difference in CD. However, if the Rep exceeds 500, CD gradually decreases with the increase in Rap. Since the separation point of the particle boundary layer moves downstream, the rough sphere experiences lower pressure in the wake vortex region. This study provides a valuable conclusion: the Rap is a non-negligible factor in studying hydrodynamic behaviors of two-phase flow, especially at high fluidization velocity.