Abstract: To investigate the synergistic wetting effect and microscopic mechanism of nonionic and anionic surfactant compounding on coal, the anthracite from Qianbei Coalfield of Guizhou Province was taken as the research object. Nonionic and anionic surfactants as well as their optimal volume ratio for compounding were optimized through sedimentation experiments. The synergistic wetting effect of the compound solution was verified by contact angle tests, and molecular dynamics simulation was employed to reveal the synergistic wetting mechanism of nonionic and anionic surfactants from the perspectives of equilibrium adsorption configuration, radial distribution function, interaction energy, relative concentration distribution and diffusion coefficient. The sedimentation experimental results show that the optimal mass fraction for both the nonionic surfactant fatty alcohol polyoxyethylene ether (JFC-U) and the anionic surfactant sodium dodecylbenzene sulfonate (SDBS) is 0.15%. When the two are compounded at a volume ratio of 1:2, the sedimentation rate of coal samples reaches the maximum, with the best synergistic wetting effect. Contact angle tests indicate that the contact angle between the JFC-U and SDBS compound solution and coal samples is 25.3°, which is lower than that of single-component solutions, verifying the synergistic wetting effect of the compound solution. Molecular dynamics simulations show that JFC-U molecules are embedded in the gaps of SDBS hydrophilic group clusters in the compound system, making the hydrophilic base layer denser. A characteristic peak of the radial distribution function appears at 0.375 nm, indicating the existence of π–π stacking between the benzene rings of SDBS and the aromatic structure of coal, which enhances the adsorption stability of surfactants on the coal surface. Compared with the single-component JFC-U and SDBS systems, the absolute value of coal-water interaction energy in the compound system increases significantly, the diffusion coefficient of water molecules decreases, and the number of hydrogen bonds rises remarkably. This demonstrates that the combined action of JFC-U and SDBS can improve the ability of the surfactant molecular layer to form hydrogen bonds with water molecules, strengthen the interaction between coal and water, suppress the diffusion of water molecules, and enhance the adsorption and aggregation capacity of the coal surface for water molecules.