Surface roughness has an important influence on the wettability of particles. This paper is an innovative exploration to control the surface wettability of apatite and dolomite from the perspective of roughness in the background of phosphate flotation. Roughness characteristics of apatite and dolomite particles and its effects on wettability were investigated with surface roughness, contact angle measurements, and SEM analysis. The relationship between surface energy and wettability of different roughness surfaces was also discussed. The results indicated that the influence of roughness on apatite and dolomite particles showed the same regularity, and wettability increased with the increasing roughness for hydrophilic surfaces, while the wettability decreased for hydrophobic surfaces. The influence of roughness on wettability can be well explained by Wenzel and Cassie models, and the surface energy of different rough surfaces had a strong correlation with their wettability. When sodium oleate was added after acid treatment, the apatite was hydrophilic, while the dolomite was hydrophobic; the difference in wettability between them became greater as surface roughness increased. Thus, it can be predicted that the selective separation of dolomite and apatite under acid reverse flotation conditions can be strengthened by increasing the mineral surface roughness during comminution.