Despite the vast research studying the influence of stress on the physical structure, little is known whether and how stress works on the chemical structure in coals. In the present study, some insights are given by investigating the macromolecular structure evolution characteristics and mechanism of a Chinese anthracite (Ro,max = 3.6%) during deformation experiments at temperatures of 300–400 °C, confining pressure of 150 MPa, and strain rates of 2.5–20*10−6 s−1. Additional heat treatments (without stress) were also performed at the same temperature range. Revealed by vitrinite reflectance, XRD, and Raman spectroscopy, a smaller and less ordered macromolecular structure was observed within experimental conditions. Upon heating alone, Ro,max and stacking diameter (La) increased together, while stacking height (Lc) and structure ordering (ID/IG and FWHM of D and G peaks) decreased with increasing temperature, indicating structure rearrangement and relaxation. In contrast, the macromolecular structure in deformation experiments showed a two-stage evolution with decreasing strain rate. Stage 1 was characterized by the obvious decreases in Ro,max, La, and Lc, but minor changes in Raman spectra, implying stress might break in-plane and inter-layer chemical bonds at high strain rates. Stage 2 was identified by the relative increases in Ro,max, La, and FWHM of D peak, in combination with Lc, mainly indicating the generation of structural defects at low strain rates allows the aromatic layer to accommodate the stress without breakage. Our results suggest stress can act on the macromolecules directly by breaking or distorting the chemical bonds depending on the strain rate.