The inherent complexity of cellulose, hemicellulose, and lignin contributes to the recalcitrance of lignocellulosic biomass, resulting in a low conversion efficiency and high cost of bioethanol conversion. Pretreatment methods that disrupt the plant cell structure of lignocellulose, such as straw, can significantly enhance the conversion efficiency. In this study, we utilized an acid-assisted mechanocatalytic depolymerization technique to pretreat rice straw, and the results demonstrated a significant disruption of the cellulose structure of the straw. Compared to the untreated straw, the particle size of pretreated straw reduced from 279 μm to 11.8 μm, the crystallinity of cellulose decreased from 43.05% to 22.71%, the specific surface area increased by 177%, and the surface oxygen-to-carbon ratio (O/C) ratio was enhanced by 75%. The changes in microstructure enabled the pretreated straw to achieve a total sugar yield of over 95% within 12 h of enzymatic hydrolysis, significantly superior to the 36.24% yield from untreated straw, the 45.20% yield from acid impregnated straw, and the 73.25% yield from ball milled straw. Consequently, acid-assisted mechanocatalytic depolymerization emerges as a highly effective pretreatment strategy to enhance both the enzymatic hydrolysis and the overall conversion efficiency of rice straw.