Our previous work has reported the pretreatment of secondary sludge with free ammonia (NH3, FA) enhanced the methane production in batch biochemical methane potential tests. However, the batch biochemical methane potential test could only provide conservative results compared to continuous/semi-continuous anaerobic digestion. Also, the impacts of FA pretreatment on the key anaerobic digestion parameters, including volatile solids (VS) destruction, sludge dewaterability and pathogen removal, are still unknown. This study for the first time investigated these impacts using semi-continuous anaerobic digestion systems for 130 days. Pretreatment of secondary sludge for 24 h at an FA concentration of 560 mg NH3-N/L improved VS destruction by 26.4% (from 22.0 to 27.8%), supported by a similar increase of 28.6% in methane production (from 126.7 to 162.9 ml CH4/g VSfed). Model based analysis revealed that FA pretreatment improved the sludge degradability extent, which may be the reason for the enhanced VS destruction. Equally importantly, the dewaterability of the digested sludge with FA pretreatment was also enhanced by 9.2% (from 12.0 to 13.1% in solids content of the dewatered digested sludge), which could be partly attributed to the increased zeta potential from -16.7 to -14.5 mV. Anaerobic digestion with FA pretreatment enhanced the removals of Fecal Coliform and E. Coli by 1.3 and 1.4 log MPN/g TS (MPN: Most Probable Number; TS: Total Solids), indicating FA pretreatment was effective in enhancing pathogen removal. With inorganic solids representing 21% of the sludge used, the volume of dewatered sludge to be disposed of was reduced by 14.5% via FA pretreatment. This will substantially decrease the cost as evaluated by economic analysis. In brief, this study provides a promising strategy to enhance sludge reduction in anaerobic digestion and is of great significance in promoting the application of FA pretreatment strategy in the real world.