In this study, cotton fabric-reinforced phenolic resin (CPF) composites were modified by adding four two-dimensional fillers: graphitic carbon nitride (g-C3N4), graphite (Gr), molybdenum disulfide (MoS2), and hexagonal boron nitride (h-BN). The tribological properties of these modified materials were investigated under dry friction and water lubrication conditions. The CPF/Gr composite exhibits significantly better tribological performance than the other three filler-modified CPF composites under dry friction, with a 24% reduction in friction coefficient and a 78% reduction in wear rate compared to the unmodified CPF composite. Under water lubrication conditions, all four fillers did not significantly alter the friction coefficient of the CPF composites. However, except for an excessive amount of Gr, the other three fillers can reduce the wear rate. Particularly in the case of 10% MoS2 content, the wear rate decreased by 56%. Scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS) were employed for the analysis of the morphology and composition of the transfer films. Additionally, molecular dynamics (MD) simulations were conducted to investigate the adsorption effects of CPF/Gr and CPF/MoS2 composites on the counterpart surface under both dry friction and water lubrication conditions. The difference in the adsorption capacity of CPF/Gr and CPF/MoS2 composites on the counterpart, as well as the resulting formation of transfer films, accounts for the variation in tribological behavior between CPF/Gr and CPF/MoS2 composites. By combining the lubrication properties of MoS2 and Gr under dry friction and water lubrication conditions and using them as co-fillers, we can achieve a synergistic lubrication effect.