Thermal hydrolysis pretreatment (THP) combined with autothermal thermophilic aerobic digestion (ATAD) process is a novel technology to achieve rapid stabilization of high solid sludge. In this study, the molecular transformation pathway of dissolved organic matter (DOM) during THP-ATAD process was analyzed by Fourier transform-ion cyclotron resonance mass spectrometry (FT-ICR-MS). The findings indicated that the removal of volatile solids from sludge containing 15% total solids achieved a rate of 40.3% following 6 d of ATAD treatment, facilitated by the conducive biodegradation environment established during the THP stage. Specifically, THP removed 24.22% of the O/C compounds and produced 45.66% of reduced organic matter. ATAD process effectively harnessed these reduced compounds from the THP stage, leading to the mineralization of organic matter through deamination and oxidation reactions, which was reflected by a 59.84-fold increase in the humification index. This work provides in-depth mechanistic insights into the transformation of organic matter during high solid sludge stabilization.