This study reported a novel and efficient approach to improve the anaerobic fermentation performance of waste activated sludge (WAS) by the indigenous iron activated persulfate (PS/Fe) treatment. Firstly, the production of short-chain fatty acids (SCFAs), especially acetic acid, was remarkably enhanced within shorter fermentation time. Mechanism investigations demonstrated that the PS/Fe treatment could simultaneously accelerate and enhance the hydrolysis and acidification process while inhibit the methanogenesis during WAS fermentation. The activities of key enzymes and the abundances of anaerobic microorganisms responsible for SCFAs production were stimulated in the presence of PS/Fe which would promote the biological processes. Secondly, the PS/Fe treatment improved the quality of fermentation residue by reducing the toxic organic compounds in the residue and enhancing the dewaterability of fermented sludge, which was beneficial to the final disposal of WAS with added economical and environmental values.