Polytetrafluoroethylene (PTFE) has a low friction coefficient but poor wear resistance (k ∼ 10−3 mm3/Nm) against various surfaces. Early mechanical modeling suggests the enhanced anti-wear performance of PTFE composites (k ∼ 10−5 mm3/Nm) relies on preferential load support by fillers. Recent studies found that tribochemical polarization of PTFE could trigger the formation of highly protective transfer films, thus resulting in exceptionally low wear-rates (k ∼ 10−7 mm3/Nm) in certain composites. Although tribochemical interactions were believed to play an important role in the wear reduction mechanisms, the atomistic details have yet to be fully described. Environmental and computational experiments in this study allowed detailed mechanistic investigations of four representative metal-, ceramic-, carbon-, and polymer-filled PTFE composites. Results found that (1) in dry argon environment, filler load support and composite microstructure dominate the wear resistance and (2) in humid air, the formation of a protective, polarized transfer film could further reduce composite wear-rate by tenfold or more. Density-functional theory (DFT) calculations supported the hypothesis that strong electrophilic atoms at certain solid surfaces tend to mechanochemically defluorinate PTFE molecule, which leads to tribochemical production and accumulation of polarized PTFE near the sliding surfaces. Molecular dynamics simulations suggested that the strengthening of nonbonding interactions (e.g., electrostatic, hydrogen-bonding) by polar polymer filler (i.e., PAI) or carboxylated PTFE could improve transfer film cohesion and adhesion strength, which was likely responsible for the additional wear reduction in humid air for certain PTFE composites. The relation between the atomistic interactions and the macroscopic wear behavior of composites was systematically discussed.